COVID-19 drug repurposing research: Difference between revisions

Content deleted Content added

Inline

Revision as of 07:11, 24 January 2022

Drug repositioning (also known as drug repurposing, re-profiling, re-tasking, or therapeutic switching) is the repurposing of an approved drug for the treatment of a different disease or medical condition than that for which it was originally developed.^[1] This is one line of scientific research which is being pursued to develop safe and effective COVID‑19 treatments.^[2]^[3] Other research directions include the development of a COVID‑19 vaccine^[4] and convalescent plasma transfusion.^[5]

Several existing antiviral medications, previously developed or used as treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), HIV/AIDS, and malaria, have been researched as potential COVID‑19 treatments, with some moving into clinical trials.^[6]^[7]^[8]

In a statement to the journal Nature Biotechnology in February 2020, US National Institutes of Health Viral Ecology Unit chief Vincent Munster said, "The general genomic layout and the general replication kinetics and the biology of the MERS, SARS and [SARS-CoV-2] viruses are very similar, so testing drugs which target relatively generic parts of these coronaviruses is a logical step".^[2]

Background

Outbreaks of novel emerging infections such as COVID‑19 pose unique challenges to discover treatments appropriate for clinical use, given the small amount of time available for drug discovery.^[9] Since the process of developing and licensing a new drug for COVID‑19 was expected to pose a particularly long delay, researchers have been probing the existing compendium of approved antivirals and other drugs as a cost-effective strategy in the meantime.^[9] In early 2020 hundreds of hospitals and universities began their own trials of existing safe drugs with repurposing potential against COVID‑19.^[10]

Drug repurposing usually requires three steps before taking the drug across the development pipeline: recognition of the right drug; systematic evaluation of the drug effect in clinical models; and estimation of usefulness in phase II clinical trials.^[11]

One approach used in repositioning is to look for drugs that act through virus-related targets such as the RNA genome (i.e. remdesivir). Another approach concerns drugs acting through polypeptide packing (i.e. lopinavir).^[9]

The rush to publish papers about the pandemic resulted in some scandals of inaccurate scientific publications.^[12]

Monoclonal antibodies

Monoclonal antibodies under investigation for repurposing include anti-IL-6 agents (tocilizumab)^[13] and anti-IL-8 (BMS-986253).^[14] (This is in parallel to novel monoclonal antibody drugs developed specifically for COVID‑19.)

Mavrilimumab is a human monoclonal antibody that inhibits human granulocyte macrophage colony-stimulating factor receptor (GM-CSF-R).^[15]^[16] It has been studied to see if it can improve the prognosis for patients with COVID‑19 pneumonia and systemic hyperinflammation. One small study indicated some beneficial effects of treatment with mavrilimumab compared with those who were not.^[17]

In January 2021, the UK National Health Service issued guidance that the immune modulating drugs tocilizumab and sarilumab were beneficial when given promptly to people with COVID‑19 admitted to intensive care, following research which found a reduction in the risk of death by 24%.^[18]

Tocilizumab

Tocilizumab is an interleukin 6 inhibitor authorized for use in several conditions, including rheumatoid arthritis, giant cell arteritis, systemic juvenile idiopathic arthritis and severe cytokine release syndrome.^[19] Its use has been studied in a number of trials.^{[citation needed]}

Hoffmann–La Roche and the WHO have run separate trials in severe cases.^[20] Roche announced on 29 July 2020, that its randomized double-blind trial of tocilizumab for the treatment of pneumonia in Covid patients had shown no benefits.^[21]

The REMAP‑CAP study in the UK found that tocilizumab was beneficial in adults with severe COVID‑19, who were critically ill and receiving respiratory or cardiovascular organ support in an intensive care setting, when this was started within 24 hours of the need for organ support.^[19] The use of tocilizumab and its place in therapy have been updated by UK NICE in January 2021.^[19]

It has been part of the large RECOVERY Trial in the UK.^[13] The published results have been reviewed as the most definitive evidence addressing the controversy over whether tocilizumab should be included in treatment for severely ill patients with COVID‑19.^[22] Over 4000 adults were randomly assigned to tocilizumab or usual care, several times more than the total in previous randomised trials, and most patients received systemic corticosteroids. Mortality within 28 days was 31% in patients allocated to tocilizumab and 35% in those receiving usual care (rate ratio 0·85; p=0·0028). Discharge from the hospital within 28 days was also more likely.^[22]

In June 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for tocilizumab for the treatment of COVID‑19 in hospitalized people aged two years of age and older who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).^[23]^[24]^[25]

As of August 2021^[update], the European Medicines Agency (EMA) is evaluating tocilizumab to extend its use to include treatment of hospitalized adults with severe COVID‑19 who are already receiving treatment with corticosteroids and require extra oxygen or mechanical ventilation (breathing assisted by a machine).^[26]

Anticoagulants

Medications to prevent blood clotting have been suggested for treatment, and anticoagulant therapy with low-molecular-weight heparin appears to be associated with better outcomes in severe COVID‐19 showing signs of coagulopathy (elevated D-dimer).^[27] Several anticoagulants have been tested in Italy, with low-molecular-weight heparin being widely used to treat patients, prompting the Italian Medicines Agency to publish guidelines on its use.^[28]^[29]

Scientists have identified an ability of heparin to bind to the spike protein of the SARS-CoV-2 virus, neutralising it, and proposed the drug as a possible antiviral.^[30]

A multicenter study on 300 patients researching the use of enoxaparin sodium at prophylaxis and therapeutic dosages was announced in Italy on 14 April.^[31]

The anticoagulant dipyridamole is proposed as a treatment for COVID‑19,^[32] and a clinical trial is underway.^[33]

Antidepressants

Many antidepressants have anti-inflammatory properties. An observational study in Paris area hospitals found that COVID‑19 patients admitted to the hospital who were already taking an antidepressant had 44% less risk of intubation or death.^[34]^[35]

Fluvoxamine

In October 2021, a large clinical trial in Brazil reported that treating high-risk outpatients with an early diagnosis of COVID‑19 with 100 mg fluvoxamine twice daily for 10 days reduced by up to about 65% the risk of hospitalization. The effect was reduced to about 32% with low adherence, possibly due to intolerance. There was also a reduction in the number of deaths by up to about 90% with high adherence. The drug was studied because of its anti-inflammatory effects, but the mechanism of action against COVID‑19 remains uncertain.^[36]^[37]^[38]

On 23 December, under very low certainty evidence, the Ontario clinical practice guideline suggested considering the drug to treat mildly ill patients within 7 days of symptom onset.^[39]

Antiparasitics

The idea of repurposing host-directed drugs for antiviral therapy has experienced a renaissance.^[40] In some cases the research has highlighted fundamental limitations to their use for the treatment of acute RNA virus infections.^[41] Antiparasitics that have been investigated include chloroquine,^[42] hydroxychloroquine,^[43] mefloquine,^[44]^[45] ivermectin,^[46] and atovaquone.^[47]

Chloroquine and hydroxychloroquine

Chloroquine and hydroxychloroquine are anti-malarial medications also used against some auto-immune diseases.^[48] Chloroquine, along with hydroxychloroquine, was an early experimental treatment for COVID-19.^[49] Neither drug has been useful to prevent or treat SARS-CoV-2 infection.^[50]^[51]^[52]^[53]^[54]^[55] Administration of chloroquine or hydroxychloroquine to COVID-19 patients has been associated with increased mortality and adverse effects, such as QT prolongation.^[56]^[57] Researchers estimate that off-label use of hydroxychloroquine in hospitals during the first phase of the pandemic caused 17,000 deaths worldwide.^[58] The widespread administration of chloroquine or hydroxychloroquine, either as monotherapies or in conjunction with azithromycin, has been associated with deleterious outcomes, including QT interval prolongation. As of 2024,^[update] scientific evidence does not substantiate the efficacy of hydroxychloroquine, with or without the addition of azithromycin, in the therapeutic management of COVID-19.^[56]

Cleavage of the SARS-CoV-2 S2 spike protein required for viral entry into cells can be accomplished by proteases TMPRSS2 located on the cell membrane, or by cathepsins (primarily cathepsin L) in endolysosomes.^[59] Hydroxychloroquine inhibits the action of cathepsin L in endolysosomes, but because cathepsin L cleavage is minor compared to TMPRSS2 cleavage, hydroxychloroquine does little to inhibit SARS-CoV-2 infection.^[59]

Several countries initially used chloroquine or hydroxychloroquine for treatment of persons hospitalized with COVID-19 (as of March 2020), though the drug was not formally approved through clinical trials.^[60]^[61] From April to June 2020, there was an emergency use authorization for their use in the United States,^[62] and was used off label for potential treatment of the disease.^[63] On 24 April 2020, citing the risk of "serious heart rhythm problems", the FDA posted a caution against using the drug for COVID-19 "outside of the hospital setting or a clinical trial".^[64]

Their use was withdrawn as a possible treatment for COVID-19 infection when it proved to have no benefit for hospitalized patients with severe COVID-19 illness in the international Solidarity trial and UK RECOVERY Trial.^[65]^[66] On 15 June 2020, the FDA revoked its emergency use authorization, stating that it was "no longer reasonable to believe" that the drug was effective against COVID-19 or that its benefits outweighed "known and potential risks".^[67]^[68]^[69] In fall of 2020, the National Institutes of Health issued treatment guidelines recommending against the use of hydroxychloroquine for COVID-19 except as part of a clinical trial.^[48]

In 2021, hydroxychloroquine was part of the recommended treatment for mild cases in India.^[70]

In 2020, the speculative use of hydroxychloroquine for COVID-19 threatened its availability for people with established indications (malaria and auto-immune diseases).^[52]

Ivermectin

Ivermectin is an antiparasitic drug that is well established for use in animals and people.^[71] The World Health Organization (WHO),^[72] the European Medicines Agency (EMA),^[73] the United States Food and Drug Administration (FDA),^[74] and the Infectious Diseases Society of America (IDSA)^[75] all advise against using ivermectin in an attempt to treat or prevent COVID-19.

Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19.^[76] Online misinformation campaigns and advocacy boosted the drug's profile among the public. While scientists and physicians largely remained skeptical, some nations adopted ivermectin as part of their pandemic-control efforts. Some people, desperate to use ivermectin without a prescription, took veterinary preparations, which led to shortages of supplies of ivermectin for animal treatment. The FDA responded to this situation by saying "You are not a horse" in a Tweet to draw attention to the issue, which they were later sued for.^[77]^[78]

Subsequent research failed to confirm the utility of ivermectin for COVID-19,^[79]^[80] and in 2021 it emerged that many of the studies demonstrating benefit were faulty, misleading, or fraudulent.^[81]^[82] Nevertheless, misinformation about ivermectin continued to be propagated on social media and the drug remained a cause célèbre for anti-vaccinationists and conspiracy theorists.^[83]

Antivirals

Research is focused on repurposing approved antiviral drugs that have been previously developed against other viruses, such as MERS-CoV, SARS-CoV, and West Nile virus.^[84] These include favipiravir,^[84] remdesivir,^[85] ribavirin,^[86] triazavirin,^[87] and umifenovir.^[88]

The combination of artesunate/pyronaridine was found to have an inhibitory effect on SARS-CoV-2 in vitro tests using Hela cells. Artesunate/pyronaridine showed a virus titer inhibition rate of 99% or more after 24 hours, while cytotoxicity was also reduced.^[89] A preprint published in July 2020, reported that pyronaridine and artesunate exhibit antiviral activity against SARS-CoV-2 and influenza viruses using human lung epithelial (Calu-3) cells.^[90] It is in phase II clinical trial in South Korea^[91]^[92]^[93] and in South Africa.^[94]

GS-441524 is the nucleoside of the ProTide remdesivir. It has been shown to cure cats infected with Feline infectious peritonitis (FIP), a feline form of coronavirus with a 96% cure rate.^[95]^[96] Studies have shown that even when remdesivir is administered, GS-441524 is the predominant metabolite circulating in serum due to rapid hydrolysis of the remdesivir pro-drugs, followed by dephosphorylation.^[97]^[98]^[99]^[100]^{[unreliable medical source?]} Some researchers have suggested its utility as a treatment for COVID‑19,^[97]^[101]^[102]^[103]^[104] noting easier synthesis, lack of first-pass metabolism in the liver, greater hydrophilicity and triphosphate formation in cell types irrespective of expression CES1 and CTSA, the enzymes required to bioactivate remdesivir.

Molnupiravir is a drug developed to treat influenza. It is in Phase III trials as a treatment for COVID‑19.^[105]^[106]^[107]^[108]^[109] In December 2020, scientists reported that the antiviral drug molnupiravir developed for the treatment of influenza can completely suppress SARS-CoV-2 transmission within 24 hours in ferrets whose COVID‑19 transmission they find to closely resemble SARS-CoV-2 spread in human young-adult populations.^[110]^[111] A clinical trial, which has not as of 1 October 2021 been peer reviewed, suggests molnupiravir taken orally can reduce the risk of hospitalization and prevent death in patients diagnosed with COVID‑19. The drug needs to be given early to be effective.^[112]^[113] As of 1 January 2022, Molnupirafir has been approved for emergency use against COVID-19 in the United Kingdom, India, and the United States.^[114]

Niclosamide was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.^[115]

Protease inhibitors, which specifically target the protease 3CLpro, are being researched and developed in the laboratory such as CLpro-1, GC376, and Rupintrivir.^[116]^[117]^[118]

Coronaviruses species possess an intrinsic resistance to ribavirin.^[119]

Sofosbuvir/daclatasvir is a drug combination developed to treat hepatitis C. In October 2020, a meta-analysis found a significantly lower risk of all-cause mortality with the drug combination when given to hospitalized patients.^[120]

Favipiravir

Favipiravir is an antiviral drug approved for the treatment of influenza in Japan.^[121]^[84] There is limited evidence suggesting that, compared to other antiviral drugs, favipiravir might improve outcomes for people with COVID‑19, but more rigorous studies are needed before any conclusions can be drawn.^[122]

Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir was "clearly effective".^[123] Of 35 patients in Shenzhen tested negative in a median of 4 days, while the length of illness was 11 days in the 45 patients who did not receive it.^[124] In a study conducted in Wuhan on 240 patients with pneumonia half were given favipiravir and half received umifenovir. The researchers found that patients recovered from coughs and fevers faster when treated with favipiravir, but that there was no change in how many patients in each group progressed to more advanced stages of illness that required treatment with a ventilator.^[125]

On 22 March 2020, Italy approved the drug for experimental use against COVID‑19 and began conducting trials in the three regions most affected by the disease.^[126] The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.^[127]

On 30 May 2020, the Russian Health Ministry approved a generic version of favipiravir named Avifavir, which proved highly effective in the first phase of clinical trials.^[128]^[129]^[130]

In June 2020, India approved the use of a generic version of favipravir called FabiFlu, developed by Glenmark Pharmaceuticals, in the treatment of mild to moderate cases of COVID‑19.^[131]

On 26 May 2021, a systematic review found a 24% greater chance of clinical improvement when administered in the first seven days of hospitalization, but no statistically significant reduction in mortality for any of the groups, including hospitalized patients and those with mild or moderate symptoms.^[132]^[133]

Lopinavir/ritonavir

Genome of SARS-CoV-2: the grey wedges show where 3CLpro the main coronavirus protease cleaves the polyprotein.

In March 2020, the main protease (3CLpro) of the SARS-CoV-2 virus was identified as a target for post-infection drugs. The enzyme is essential for processing the replication-related polyprotein. To find the enzyme, scientists used the genome published by Chinese researchers in January 2020 to isolate the main protease.^[134] Protease inhibitors approved for treating human immunodeficiency viruses (HIV) – lopinavir and ritonavir – have preliminary evidence of activity against the coronaviruses, SARS and MERS.^[6]^[135] As a potential combination therapy, they are used together in two Phase III arms of the 2020 global Solidarity project on COVID‑19.^[135]^[136] A preliminary study in China of combined lopinavir and ritonavir found no effect in people hospitalized for COVID‑19.^[137]

One study of lopinavir/ritonavir (Kaletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".^[137]^[138] The drugs were designed to inhibit HIV from replicating by binding to the protease. A team of researchers at the University of Colorado are trying to modify the drugs to find a compound that will bind with the protease of SARS-CoV-2.^[139] There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS because such drugs are unlikely to be effective against a virus lacking the specific HIV-1 protease they target.^[2] The WHO included lopinavir/ritonavir in the international Solidarity trial.^[140]

On 29 June, the chief investigators of the UK RECOVERY Trial reported that there was no clinical benefit from use of lopinavir-ritonavir in 1,596 people hospitalized with severe COVID‑19 infection over 28 days of treatment.^[141]^[142]

A study published in October 2020, screening those FDA approved drugs which target SARS-CoV-2 spike (S) protein proposed that the current unbalanced combination formula of lopinavir might in fact interfere with the ritonavir's blocking activity on the receptor binding domain-human angiotensin converting enzyme-2 (RBD-hACE2) interaction, thus effectively limiting its therapeutic benefit in COVID‑19 cases.^[143]

Remdesivir

Remdesivir, sold under the brand name Veklury,^[144]^[145] is a broad-spectrum antiviral medication developed by the biopharmaceutical company Gilead Sciences.^[146] It is administered via injection into a vein.^[147]^[148] During the COVID‑19 pandemic, remdesivir was approved or authorized for emergency use to treat COVID‑19 in numerous countries.^[149]

Remdesivir was originally developed to treat hepatitis C,^[150] and was subsequently investigated for Ebola virus disease and Marburg virus infections^[151] before being studied as a post-infection treatment for COVID‑19.^[152]

Remdesivir is a prodrug that is intended to allow intracellular delivery of GS-441524 monophosphate and subsequent biotransformation into GS-441524 triphosphate, a ribonucleotide analogue inhibitor of viral RNA polymerase.^[153]

The most common side effect in healthy volunteers is raised blood levels of liver enzymes.^[144] The most common side effect in people with COVID‑19 is nausea.^[144] Side effects may include liver inflammation and an infusion-related reaction with nausea, low blood pressure, and sweating.^[154]

The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.^[155]

Immunosuppressants

As of July 2021^[update], the European Medicines Agency (EMA) is evaluating an application to extend the use of anakinra (Kineret) to include treatment of COVID‑19 in adults with pneumonia who are at risk of developing severe respiratory failure (inability of the lungs to work properly).^[156]

Interferons

Drugs with immune modulating effects that may prove useful in COVID‑19 treatment include type I Interferons such as Interferon-β, peginterferon alpha-2a and -2b.^[157]^[158]

IFN-β 1b have been shown in an open label randomised controlled trial in combination with lopinavir/ ritonavir and ribavirin to significantly reduce viral load, alleviate symptoms and reduce cytokine responses when compared to lopinavir/ ritonavir alone.<Lancet 2020;395(10238):1695-1704> IFN-β will be included in the international Solidarity Trial in combination with the HIV drugs Lopinavir and Ritonavir.^[157] as well as the REMAP-CAP^[158] Finnish biotech firm Faron Pharmaceuticals continues to develop INF-beta for ARDS and is involved in worldwide initiatives^[which?] against COVID‑19, including the Solidarity trial.^[159] UK biotech firm Synairgen started conducting trials on IFN-β, a drug that was originally developed to treat COPD.^[140]

Steroids

Dexamethasone

Dexamethasone is a corticosteroid medication in use for multiple conditions such as rheumatic problems, skin diseases, asthma and chronic obstructive lung disease among others.^[160] A multi-center, randomized controlled trial of dexamethasone in treating acute respiratory distress syndrome (ARDS), published in February 2020, showed reduced need for mechanical ventilation and mortality.^[161] Dexamethasone is only helpful in people requiring supplemental oxygen. Following an analysis of seven randomized trials,^[162] the WHO recommends the use of systemic corticosteroids in guidelines for treatment of people with severe or critical illness, and that they not be used in people that do not meet the criteria for severe illness.^[163]

On 16 June, the Oxford University RECOVERY Trial issued a press release announcing preliminary results that the drug could reduce deaths by about a third in participants on ventilators and by about a fifth in participants on oxygen; it did not benefit patients who did not require respiratory support. The researchers estimated that treating 8 patients on ventilators with dexamethasone saved one life, and treating 25 patients on oxygen saved one life.^[164] Several experts called for the full dataset to be published quickly to allow wider analysis of the results.^[165]^[166] A preprint was published on 22 June^[167] and the peer-reviewed article appeared on 17 July.^[168]

Based on those preliminary results, dexamethasone treatment has been recommended by the US National Institutes of Health (NIH) for patients with COVID‑19 who are mechanically ventilated or who require supplemental oxygen but are not mechanically ventilated. The NIH recommends against using dexamethasone in patients with COVID‑19 who do not require supplemental oxygen.^[169] In July 2020, the World Health Organization (WHO) stated they are in the process of updating treatment guidelines to include dexamethasone or other steroids.^[170]

The Infectious Diseases Society of America (IDSA) guideline panel suggests the use of glucocorticoids for patients with severe COVID‑19; where severe is defined as patients with oxygen saturation (SpO₂) ≤94% on room air, and those who require supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).^[171] The IDSA recommends against the use of glucocorticoids for those with COVID‑19 without hypoxemia requiring supplemental oxygen.^[171]

In July 2020, the European Medicines Agency (EMA) started reviewing results from the RECOVERY study arm that involved the use of dexamethasone in the treatment of patients with COVID‑19 admitted to the hospital to provide an opinion on the results. It focused particularly on the potential use of the drug for the treatment of adults with COVID‑19.^[172]

In September 2020, the WHO released updated guidance on using corticosteroids for COVID‑19.^[173]^[174] The WHO recommends systemic corticosteroids rather than no systemic corticosteroids for the treatment of people with severe and critical COVID‑19 (strong recommendation, based on moderate certainty evidence).^[173] The WHO suggests not to use corticosteroids in the treatment of people with non-severe COVID‑19 (conditional recommendation, based on low certainty evidence).^[173]

In September 2020, the European Medicines Agency (EMA) endorsed the use of dexamethasone in adults and adolescents (from twelve years of age and weighing at least 40 kilograms (88 lb)) who require supplemental oxygen therapy.^[175] Dexamethasone can be taken by mouth or given as an injection or infusion (drip) into a vein.^[175]

Hydrocortisone

In September 2020, a meta-analysis published by the WHO Rapid Evidence Appraisal for COVID‑19 Therapies (REACT) Working Group found hydrocortisone to be effective in reducing mortality rate of critically ill COVID‑19 patients when compared to other usual care or a placebo.^[176]

The use of corticosteroids can cause a severe and deadly "hyperinfection" syndrome for people with strongyloidiasis, which may be an underlying condition in populations exposed to the parasite Strongyloides stercoralis. This risk can be mitigated by the presumptive use of ivermectin before steroid treatment.^[177]

Budesonide

Administration of this inhaled steroid early in the course of COVID‑19 infection has been found to reduce the likelihood of needing urgent medical care and reduced the time to recovery.^[178]^[179] More studies are on-going.^[179] In April 2021, budesonide was approved by authorities in the UK for off-label use to treat COVID‑19 on a case-by-case basis.^[180]

Others

Ciclesonide, an inhaled corticosteroid for asthma, was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.^[115] It has been used for treatment of pre-symptomatic COVID‑19 patients and is under-going clinical trials.^[181]

Vitamins

Vitamin C

Supplementation with micronutrients, including vitamin C, has been suggested as part of the supportive management of COVID‑19, as levels of vitamin C in serum and leukocytes are depleted in the acute stage of infection owing to increased metabolic demands.^[182] The use of high-dose intravenous vitamin C has been studied.^[182] According to ClinicalTrials.gov, there are 50 completed or ongoing clinical trials including vitamin C, which have completed or are recruiting people, hospitalized and severely ill with COVID‑19.^[183]

A meta-analysis of six randomized clinical trials involving vitamin C treatments, using doses ranging from 50 mg/kg/day to 24 g/day given orally or intravenously, reported outcomes on mortality, hospitalization duration, intensive care duration and need for ventilation.^[184] This concluded that administration of vitamin C did not have any effect on major health outcomes in COVID-infected patients when compared to placebo or standard therapy. Sub-group analyses based on dosage, route of administration and disease severity, failed to show any observable benefits of vitamin C.^[184]

The National Institutes of Health (NIH) COVID‑19 Treatment Guidelines states "there is insufficient evidence for the COVID‑19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of vitamin C for the treatment of COVID‑19 in either critically ill or non-critically ill patients."^[185]

Vitamin D

During the COVID‑19 pandemic, there has been interest in vitamin D status and supplements, given the significant overlap in the risk factors for severe COVID‑19 and vitamin D deficiency.^[186] These include obesity, older age, and Black or Asian ethnic origin, and it is notable that vitamin D deficiency is particularly common within these groups.^[186]

The National Institutes of Health (NIH) COVID‑19 Treatment Guidelines states "there is insufficient evidence to recommend either for or against the use of vitamin D for the prevention or treatment of COVID‑19."^[187]

The general recommendation to consider taking vitamin D supplements, particularly given the levels of vitamin D deficiency in Western populations, has been repeated.^[188] As of February 2021^[update], the English National Institute for Health and Care Excellence (NICE) continued to recommend small doses of supplementary vitamin D for people with little exposure to sunshine, but recommended that practitioners should not offer a vitamin D supplement solely to prevent or treat COVID‑19, except as part of a clinical trial.^[188]

Multiple studies have reported links between pre-existing vitamin D deficiency and the severity of the disease. Several systematic reviews and meta-analyses of these show that vitamin D deficiency may be associated with a higher probability of becoming infected with COVID‑19, and have clearly demonstrated there are significant associations between deficiency and a greater severity of the disease, including relative increases in hospitalization and mortality rates of about 80%.^[189]^[190]^[191] The quality of some of the studies included and whether this demonstrates a causal relationship has been questioned.^[192]

Many clinical trials are underway or have been completed assessing the use of oral vitamin D and its metabolites such as calcifediol for prevention or treatment of COVID‑19 infection, especially in people with vitamin D deficiency.^[193]^[194]^[186]^[195]

The effects of oral vitamin D supplementation on the need for intensive care unit (ICU) admission and mortality in hospitalized COVID‑19 patients has been the subject of a meta-analysis.^[196] A much lower ICU admission rate was found in patients who received vitamin D supplementation, which was only 36% of that seen in patients without supplementation (p<0.0001).^[196] No significant effects on mortality were found in this meta-analysis.^[196] The certainty of these analyses is limited by the heterogenicity in the studies which include both vitamin D3 (cholecalciferol) and calcifediol, but these findings indicate a potential role in improving COVID‑19 severity, with more robust data being required to substantiate any effects on mortality.^[196]^[197]

Calcifediol, which is 25-hydroxyvitamin D, is more quickly activated,^[198] and has been used in several trials.^[194] Review of the published results suggests that calcifediol supplementation may have a protective effect on the risk of ICU admissions in COVID‑19 patients.^[192]

Minerals

Zinc

The National Institutes of Health (NIH) COVID‑19 Treatment Guidelines states "there is insufficient evidence to recommend either for or against the use of zinc for the treatment of COVID‑19" and that "the Panel recommends against using zinc supplementation above the recommended dietary allowance for the prevention of COVID‑19, except in a clinical trial (BIII)."^[199]

Others

A form of angiotensin-converting enzyme 2, a Phase II trial is underway with 200 patients to be recruited from severe, hospitalized cases in Denmark, Germany, and Austria to determine the effectiveness of the treatment.^[200]^[201]

Some antibiotics that have been identified as potentially repurposable as COVID‑19 treatments,^[202]^[203] including teicoplanin,^[204] oritavancin,^[205] dalbavancin,^[205] monensin,^[205] and azithromycin.^[206] New York State began trials for the antibiotic azithromycin on 24 March 2020.^[206]

On 31 July 2020, the U.S. Food and Drug Administration (FDA) authorized Revive Therapeutics to proceed with a randomized, double-blind, placebo-controlled confirmatory Phase III clinical trial protocol to evaluate the safety and efficacy of the antirheumatic agent bucillamine in patients with mild-moderate COVID‑19.^[207]

The oral JAK inhibitor baricitinib is also being studied for COVID‑19 treatment.^[208] In November 2020, the FDA granted emergency use authorization for baricitinib to be given to certain people hospitalized with suspected or confirmed COVID‑19 (specifically, adults and children two years of age or older requiring supplemental oxygen, mechanical ventilation, or ECMO), but only in conjunction with remdesivir.^[209] In a single clinical trial, this combination therapy was shown to have a small, but statistically significant effect on patient outcomes compared to administration of remdesivir alone.^[210] In April 2021, the European Medicines Agency (EMA) started evaluating the extended use of baricitinib to include treatment of COVID‑19 in hospitalized patients ten years of age and older who require supplemental oxygen.^[211] In July 2021, the FDA revised the EUA for baricitinib now authorizing it alone for the treatment of COVID‑19 in hospitalized people aged two years of age or older requiring supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO).^[212]^[213]^[214] Under the revised EUA, baricitinib is no longer required to be administered with remdesivir.^[214]

In 2021, the importance of drug repurposing for COVID‑19 led to the establishment of broad-spectrum therapeutics.^[215] Broad-spectrum therapeutics are effective against multiple types of pathogens.^[216] Such drugs have been suggested as potential emergency treatments for future pandemics.^[217]^[218]

Histamine H₂ receptor antagonists are under investigation. Cimetidine has been suggested as a treatment for COVID‑19.^[32] Famotidine has been suggested as a treatment for COVID‑19,^[32] and a clinical study is underway.^[219]

Researchers from the Montreal Heart Institute in Canada are studying the role of colchicine in reducing inflammation and pulmonary complications in patients suffering from mild symptoms of COVID‑19.^[220] The study, named COLCORONA, was recruiting 6000 adults 40 and older who were diagnosed with COVID‑19 and experienced mild symptoms not requiring hospitalization.^[220]^[221] Women who were pregnant or breastfeeding or who did not have an effective contraceptive method were not eligible. The trial results are favorable, but inconclusive.^[221]

Fenofibrate and bezafibrate have been suggested for treatment of life-threatening symptoms of COVID‑19.^[32]^[222] Fenofibrate also lowered severe progressive inflammation markers in hospitalized COVID‑19 patients within 48 hours of treatment in an Israeli study.^[223] It showed extremely promising results by interfering with how coronavirus reproduce.^[224]

A trial called "Liberate" has been started in the United Kingdom to determine the effectiveness of ibuprofen in reducing the severity and progression of lung injury which results in breathing difficulties for COVID‑19 patients. Subjects are to receive three doses of a special formulation of the drug – lipid ibuprofen – in addition to usual care.^[225]^[226]

A clinical cohort study in Brazil found that COVID‑19 patients who received a recent influenza vaccine needed less intensive care support, less invasive respiratory support, and were less likely to die.^[227]^{[unreliable medical source?]}

nanoFenretinide is nanoparticle sized fenretinide and repurposed oncology drug approved to enter the clinic for a lymphoma indication.^[228] It was identified as a candidate antiviral in an in vitro drug screening assay done in South Korea.^[115] Fenretinide's clinical safety profile also makes it an ideal candidate in combination regimens.^{[citation needed]}

Sildenafil, more commonly known by the brand name Viagra, is proposed as a treatment for COVID‑19,^[32] and a Phase III clinical trial is underway.^[229]

References

^ "Repurposing Drugs". National Center for Advancing Translational Sciences (NCATS). U.S. Department of Health & Human Services, National Institutes of Health. 7 November 2017. Retrieved 26 March 2020.
^ ^a ^b ^c Harrison C (April 2020). "Coronavirus puts drug repurposing on the fast track". Nature Biotechnology. 38 (4): 379–81. doi:10.1038/d41587-020-00003-1. PMID 32205870. S2CID 213394680.
^ Sleigh SH, Barton CL (2010). "Repurposing Strategies for Therapeutics". Pharmaceutical Medicine. 24 (3): 151–59. doi:10.1007/BF03256811. S2CID 25267555.
^ "COVID-19 Vaccine Frontrunners".
^ Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. (April 2020). "Effectiveness of convalescent plasma therapy in severe COVID-19 patients". Proceedings of the National Academy of Sciences of the United States of America. 117 (17): 9490–96. doi:10.1073/pnas.2004168117. PMC 7196837. PMID 32253318.
^ ^a ^b Li G, De Clercq E (March 2020). "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)". Nature Reviews. Drug Discovery. 19 (3): 149–50. doi:10.1038/d41573-020-00016-0. PMID 32127666.
^ "COVID-19 treatment and vaccines tracker (Choose tab of interest, apply filters to view select data)". Milken Institute. 2 June 2020. Retrieved 3 June 2020.
^ Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (April 2020). "Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review". JAMA. 323 (18): 1824–36. doi:10.1001/jama.2020.6019. PMID 32282022.
^ ^a ^b ^c Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK (December 2020). "Drug repurposing approach to fight COVID-19". Pharmacological Reports. 72 (6): 1479–1508. doi:10.1007/s43440-020-00155-6. PMC 7474498. PMID 32889701.
^ Zimmer C (30 January 2021). "How the Search for Covid-19 Treatments Faltered While Vaccines Sped Ahead". The New York Times.
^ Kirtonia A, Gala K, Fernandes SG, Pandya G, Pandey AK, Sethi G, et al. (January 2021). "Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics". Seminars in Cancer Biology. 68: 258–78. doi:10.1016/j.semcancer.2020.04.006. ISSN 1044-579X. PMID 32380233. S2CID 218556384.
^ Carbone M, Lednicky J, Xiao SY, Venditti M, Bucci E (April 2021). "Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For". Journal of Thoracic Oncology. 16 (4): 546–71. doi:10.1016/j.jtho.2020.12.014. PMC 7832772. PMID 33422679.
^ ^a ^b "RECOVERY Trial". Retrieved 17 June 2020.
^ "Anti-Interleukin-8 (Anti-IL-8) for Patients With COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.
^ "Statement On A Nonproprietary Name Adopted By The USAN Council: Mavrilimumab" (PDF). American Medical Association. Archived from the original (PDF) on 28 September 2012.
^ Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F (September 2011). "Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study". Annals of the Rheumatic Diseases. 70 (9): 1542–49. doi:10.1136/ard.2010.146225. PMC 3147227. PMID 21613310.
^ De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A, et al. (16 June 2020). "GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study". The Lancet Rheumatology. 2 (8): e465–73. doi:10.1016/S2665-9913(20)30170-3. PMC 7430344. PMID 32835256.
^ "Arthritis drugs effective in improving survival in sickest COVID-19 patients". National Institute for Health Research. 7 January 2021.
^ ^a ^b ^c "Product overview | COVID‑19 rapid evidence summary: Tocilizumab for COVID‑19 | Advice | NICE". Retrieved 20 January 2021.
^ "WHO and Roche launch trials of potential coronavirus treatments". SwissInfo.Ch. 20 March 2020. Retrieved 8 August 2020.
^ "Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia". Roche (Press release). 29 July 2020. Retrieved 18 August 2020.
^ ^a ^b Gupta S, Leaf DE (May 2021). "Tocilizumab in COVID-19: some clarity amid controversy". Lancet. 397 (10285): 1599–1601. doi:10.1016/S0140-6736(21)00712-1. PMC 8084409. PMID 33933194.
^ "Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 24 June 2021. Retrieved 24 June 2021. This article incorporates text from this source, which is in the public domain.
^ "Tocilizumab Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). June 2021. This article incorporates text from this source, which is in the public domain.
^ "Frequently Asked Questions on the Emergency Use Authorization for Actemra (tocilizumab) for Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). July 2021. This article incorporates text from this source, which is in the public domain.
^ "EMA starts evaluating use of RoActemra in hospitalised adults with severe COVID-19". European Medicines Agency (EMA) (Press release). 16 August 2021. Retrieved 24 August 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ Tang N, Bai H, Chen X, Gong J, Li D, Sun Z (May 2020). "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy". Journal of Thrombosis and Haemostasis. 18 (5): 1094–9. doi:10.1111/jth.14817. PMID 32220112.
^ "Medicines usable for treatment of COVID-19 disease". Italian Medicines Agency. Retrieved 29 March 2021.
^ "Low molecular weight heparins in the treatment of adult patients with COVID-19". AIFA Italian Medicines Agencty. 24 November 2020.
^ Weintraub A. "How COVID-19 could be crippled by an age-old blood thinner". Fierce Biotech. Retrieved 22 July 2020.
^ "Coronavirus, al via studio su eparina per 300 pazienti". Adnkronos. Retrieved 15 April 2020.
^ ^a ^b ^c ^d ^e Rogosnitzky M, Berkowitz E, Jadad AR (May 2020). "Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point". JMIR Public Health and Surveillance. 6 (2): e19199. doi:10.2196/19199. PMC 7224168. PMID 32374264.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ "Chinese Clinical Trial Register (ChiCTR) – The world health organization international clinical trials registered organization registered platform". www.chictr.org.cn.
^ Landhuis E (12 November 2021). "Investigating Antidepressants' Surprising Effect on COVID Deaths". Scientific American. Retrieved 1 December 2021.
^ Hoertel N, Sánchez-Rico M, Vernet R, Beeker N, Jannot A, Neuraz A, et al. (4 February 2021). "Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study". Molecular Psychiatry. 26 (9): 5199–5212. doi:10.1038/s41380-021-01021-4. ISSN 1476-5578. PMID 33536545. S2CID 231794088.
^ Sidik SM (October 2021). "Common antidepressant slashes risk of COVID death, study says". Nature. doi:10.1038/d41586-021-02988-4. PMID 34716441. S2CID 240229837.
^ Fox, Maggie (28 October 2021). "Cheap, generic anti-depressant may reduce severe Covid-19 disease, study finds". CNN. Retrieved 22 November 2021.
^ Reis G, Dos Santos Moreira-Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, et al. (January 2022). "Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial". The Lancet. Global Health. 10 (1): e42–e51. doi:10.1016/S2214-109X(21)00448-4. PMC 8550952. PMID 34717820.
^ Ontario COVID-19 Drugs and Biologics Clinical Practice Guidelines Working Group (23 December 2021). "Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19". Ontario COVID-19 Science Advisory Table. Version 6.0. doi:10.47326/ocsat.cpg.2021.6.0. S2CID 245441405.{{cite journal}}: CS1 maint: numeric names: authors list (link)
^ Zumla A, Rao M, Wallis RS, Kaufmann SH, Rustomjee R, Mwaba P, et al. (April 2016). "Host-directed therapies for infectious diseases: current status, recent progress, and future prospects". The Lancet. Infectious Diseases (review). 16 (4): e47–63. doi:10.1016/S1473-3099(16)00078-5. PMC 7164794. PMID 27036359.
^ Sourimant J, Aggarwal M, Plemper RK (August 2021). "Progress and pitfalls of a year of drug repurposing screens against COVID-19". Current Opinion in Virology. 49: 183–193. doi:10.1016/j.coviro.2021.06.004. PMC 8214175. PMID 34218010.
^ Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (March 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408. PMID 32020029.
^ Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. (March 2020). "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial". International Journal of Antimicrobial Agents. 56 (1): 105949. doi:10.1016/j.ijantimicag.2020.105949. PMC 7102549. PMID 32205204.
^ Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, et al. (October 2020). "Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo". J Virol. 94 (21). doi:10.1128/JVI.01218-20. PMC 7565640. PMID 32817221.
^ "ФМБА России: доказана противовирусная активность "Мефлохина" в отношении возбудителя COVID-19" (in Russian). Federal Biomedical Agency. 10 April 2020. Retrieved 11 April 2020.
^ Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (April 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.
^ "Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection". ClinicalTrials.gov. Retrieved 10 September 2020.
^ ^a ^b "Chloroquine or Hydroxychloroquine". COVID-19 Treatment Guidelines. National Institutes of Health. Archived from the original on 28 August 2020. Retrieved 14 February 2021.
^ "Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020". FDA. 30 March 2020. Archived from the original on 19 October 2020. Retrieved 28 February 2021.
^ Smit M, Marinosci A, Agoritsas T, Calmy A (April 2021). "Prophylaxis for COVID-19: a systematic review". Clinical Microbiology and Infection (Systematic review). 27 (4): 532–537. doi:10.1016/j.cmi.2021.01.013. PMC 7813508. PMID 33476807.
^ Meyerowitz EA, Vannier AG, Friesen MG, Schoenfeld S, Gelfand JA, Callahan MV, Kim AY, Reeves PM, Poznansky MC (May 2020). "Rethinking the role of hydroxychloroquine in the treatment of COVID-19". FASEB Journal. 34 (5): 6027–6037. doi:10.1096/fj.202000919. PMC 7267640. PMID 32350928.
^ ^a ^b Juurlink DN (April 2020). "Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection". CMAJ. 192 (17): E450–E453. doi:10.1503/cmaj.200528. PMC 7207200. PMID 32269021.
^ "Assessment of Evidence for COVID-19-Related Treatments: Updated 4/3/2020". American Society of Health-System Pharmacists. Archived from the original on 14 April 2021. Retrieved 7 April 2020.
^ Yazdany J, Kim AH (June 2020). "Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know". Annals of Internal Medicine. 172 (11): 754–755. doi:10.7326/M20-1334. PMC 7138336. PMID 32232419.
^ Singh, Bhagteshwar; Ryan, Hannah; Kredo, Tamara; Chaplin, Marty; Fletcher, Tom (12 February 2021). Cochrane Infectious Diseases Group (ed.). "Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19". Cochrane Database of Systematic Reviews. 2021 (2): CD013587. doi:10.1002/14651858.CD013587.pub2. PMC 8094389. PMID 33624299.
^ ^a ^b Nag K, Tripura K, Datta A, Karmakar N, Singh M, Singh M, Singal K, Pradhan P (2024). "Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review". Indian J Community Med. 49 (1): 22–27. doi:10.4103/ijcm.ijcm_983_22. PMC 10900474. PMID 38425958.
^ Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai M (2020). "QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review". Heart Rhythm. 17 (9): 1472–1479. doi:10.1016/j.hrthm.2020.05.008. PMC 7211688. PMID 32438018.
^ Pradelle, Alexiane; Mainbourg, Sabine; Provencher, Steeve; Massy, Emmanuel; Grenet, Guillaume; Lega, Jean-Christophe (February 2024). "Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate". Biomedicine & Pharmacotherapy. 171. doi:10.1016/j.biopha.2023.116055. PMID 38171239. S2CID 266754199.
^ ^a ^b Jackson CB, Farzan M, Chen B, Choe H (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology. 23 (1): 3–20. doi:10.1038/s41580-021-00418-x. PMC 8491763. PMID 34611326.
^ "Information for clinicians on therapeutic options for COVID-19 patients". US Centers for Disease Control and Prevention. 21 March 2020. Archived from the original on 8 April 2020. Retrieved 22 March 2020.
^ Hinton DM (28 March 2020). "Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original on 2 October 2020. Retrieved 30 March 2020.
^ "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. 11 February 2020. Archived from the original on 8 April 2020. Retrieved 9 April 2020.
^ Kalil AC (May 2020). "Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics". JAMA. 323 (19): 1897–1898. doi:10.1001/jama.2020.4742. PMID 32208486.
^ "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020. Archived from the original on 4 November 2020. Retrieved 28 February 2021.
^ Mulier T (17 June 2020). "Hydroxychloroquine halted in WHO-sponsored COVID-19 trials". Bloomberg. Archived from the original on 11 October 2020. Retrieved 17 June 2020.
^ "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 5 June 2020. Archived from the original on 8 October 2020. Retrieved 7 June 2020.
^ "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine". U.S. Food and Drug Administration (FDA) (Press release). 15 June 2020. Archived from the original on 15 June 2020. Retrieved 15 June 2020.
^ Lovelace Jr B (15 June 2020). "FDA revokes emergency use of hydroxychloroquine". CNBC. Archived from the original on 11 October 2020. Retrieved 28 February 2021.
^ "Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate" (PDF). U.S. Food and Drug Administration (FDA). 15 June 2020. Archived from the original on 15 April 2021. Retrieved 15 June 2020.
^ "Clinical Management Protocol for Covid-19 (in Adults)" (PDF). Ministry of Health and Family Welfare. 24 May 2021. Archived (PDF) from the original on 5 December 2021. Retrieved 10 July 2021. "Health ministry issues revised clinical management protocols for Covid-19 amid spurt in cases". Times of India. Press Trust of India. 13 June 2021. Archived from the original on 11 July 2021. Retrieved 10 July 2021.
^ Tafoya QJ (2021). "Appendix – COVID-19-Directed Medications". In Ramadan AR, Gamaleldin O (eds.). Neurological Care and the COVID-19 Pandemic (1st ed.). Elsevier. pp. 173–174. doi:10.1016/B978-0-323-82691-4.00016-9. ISBN 978-0-323-82691-4. S2CID 239763031. The WHO, the European Medicines Agency, and the IDSA all recommend against the use of ivermectin for treatment of COVID-19, with the NIH stating that there is insufficient data to recommend for or against its use outside the context of a clinical trial.
^ "WHO advises that ivermectin only be used to treat COVID-19 within clinical trials". Newsroom. World Health Organization. Geneva, Switzerland. 31 March 2021. Retrieved 12 May 2023.
^ "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". News. European Medicines Agency. Amsterdam. 22 March 2021. Retrieved 12 May 2023.
^ "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19". United States Food and Drug Administration. Consumer Updates. Silver Spring, Maryland: Food and Drug Administration. 10 December 2021. Retrieved 12 May 2023.
^ "IDSA Guidelines on the Treatment and Management of Patients with COVID-19: Recommendations 23-24: Ivermectin". Infectious Diseases Society of America. IDSA Practice Guidelines. Arlington, Virginia. 11 April 2023. Retrieved 12 May 2023.
^ Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (June 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.
^ Woo E (28 September 2021). "How Covid Misinformation Created a Run on Animal Medicine". New York Times. Archived from the original on 7 January 2022. Retrieved 23 December 2021.
^ Langford C (1 September 2023). "Fifth Circuit sides with ivermectin-prescribing doctors in their quarrel with the FDA". Courthouse News Service.
^ Popp M, Reis S, Schießer S, Hausinger RI, Stegemann M, Metzendorf MI, Kranke P, Meybohm P, Skoetz N, Weibel S (June 2022). "Ivermectin for preventing and treating COVID-19". Cochrane Database Syst Rev (Systematic review). 2022 (6): CD015017. doi:10.1002/14651858.CD015017.pub3. PMC 9215332. PMID 35726131.
^ Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, Dos Santos CV, Campos VH, Nogueira AM, de Almeida AP, Callegari ED, Neto AD, Savassi LC, Simplicio MI, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ (May 2022). "Effect of Early Treatment with Ivermectin among Patients with Covid-19". N Engl J Med (Randomized controlled trial). 386 (18): 1721–1731. doi:10.1056/NEJMoa2115869. PMC 9006771. PMID 35353979.
^ Lawrence JM, Meyerowitz-Katz G, Heathers JA, Brown NJ, Sheldrick KA (November 2021). "The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable". Nature Medicine. 27 (11): 1853–1854. doi:10.1038/s41591-021-01535-y. PMID 34552263. S2CID 237607620.
^ "Ivermectin: How false science created a Covid 'miracle' drug". BBC News. 6 October 2021. Archived from the original on 8 January 2022. Retrieved 26 December 2021.
^ Melissa Davey (15 July 2021). "Huge study supporting ivermectin as Covid treatment withdrawn over ethical concerns". The Guardian. Archived from the original on 16 January 2022. Retrieved 12 May 2023.
^ ^a ^b ^c Dong L, Hu S, Gao J (2020). "Discovering drugs to treat coronavirus disease 2019 (COVID-19)". Drug Discoveries & Therapeutics. 14 (1): 58–60. doi:10.5582/ddt.2020.01012. PMID 32147628.
^ Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. (May 2020). "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial". Lancet. 395 (10236): 1569–78. doi:10.1016/S0140-6736(20)31022-9. PMC 7190303. PMID 32423584.
^ Lu CC, Chen MY, Lee WS, Chang YL (2020). "Potential therapeutic agents against COVID-19: What we know so far". J Chin Med Assoc. 83 (6): 534–36. doi:10.1097/JCMA.0000000000000318. PMC 7176266. PMID 32243270.
^ Wu X, Yu K, Wang Y, Xu W, Ma H, Hou Y, et al. (July 2020). "The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol". Engineering (Beijing). 6 (10): 1199–204. doi:10.1016/j.eng.2020.06.011. PMC 7332434. PMID 32837750.
^ Lu H (March 2020). "Drug treatment options for the 2019-new coronavirus (2019-nCoV)". Bioscience Trends. 14 (1): 69–71. doi:10.5582/bst.2020.01020. PMID 31996494.
^ "'Pyramax' drug repurposing?... targets COVID-19 treatment". Doctor's News. Retrieved 25 June 2020.
^ Bae JY, Lee GE, Park H, Cho J, Kim YE, Lee JY, et al. (2020). "Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza". bioRxiv. doi:10.1101/2020.07.28.225102. S2CID 220885187.
^ "COVID-19: Pyramax Enters Phase II Clinical Trial in South Korea". www.pharmanewsonline.com. Retrieved 17 June 2020.
^ "A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase II Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". nedrug.mfds.go.kr. Retrieved 25 June 2020.
^ "The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". ClinicalTrials.gov. Retrieved 10 September 2020.
^ "COVID-19 Treatment in South Africa". ClinicalTrials.gov. Retrieved 21 September 2020.
^ Zhang S (8 May 2020). "A Much-Hyped COVID-19 Drug Is Almost Identical to a Black-Market Cat Cure". The Atlantic.
^ Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, et al. (April 2019). "Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis". Journal of Feline Medicine and Surgery. 21 (4): 271–81. doi:10.1177/1098612X19825701. PMC 6435921. PMID 30755068.
^ ^a ^b Yan VC, Muller FL (July 2020). "Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment". ACS Medicinal Chemistry Letters. 11 (7): 1361–66. doi:10.1021/acsmedchemlett.0c00316. PMC 7315846. PMID 32665809.
^ Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. (March 2016). "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys". Nature. 531 (7594): 381–85. Bibcode:2016Natur.531..381W. doi:10.1038/nature17180. PMC 5551389. PMID 26934220.
^ Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. (June 2017). "Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses". Science Translational Medicine. 9 (396): eaal3653. doi:10.1126/scitranslmed.aal3653. PMC 5567817. PMID 28659436.
^ Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. (April 2020). "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2". bioRxiv: 2020.04.15.043166. doi:10.1101/2020.04.15.043166. PMC 7239049. PMID 32511319.
^ "Gilead should ditch remdesivir and focus on its simpler ancestor". Stat. 14 May 2020. Retrieved 5 June 2020.
^ Yan VC, Muller FL (14 May 2020). "Gilead should ditch remdesivir and focus on its simpler and safer ancestor". Statnews.
^ Westgate J (7 May 2020). "Vet science 'being ignored' in quest for COVID-19 drug". Vet Times. Retrieved 28 July 2020.
^ Avoxa-Mediengruppe Deutscher Apotheker GmbH. "Verwandtschaft ersten Grades: Remdesivir-Metabolit noch schärfere Waffe gegen Covid-19?". Pharmazeutische Zeitung online (in German).
^ "Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013)". ClinicalTrials.gov. 25 June 2021. Retrieved 18 October 2021.
^ "Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001)". ClinicalTrials.gov. 5 October 2020. Retrieved 18 October 2021.
^ "Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)". ClinicalTrials.gov. 5 October 2020. Retrieved 18 October 2021.
^ "A Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.
^ "The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID)". ClinicalTrials.gov. Retrieved 10 September 2020.
^ "Oral drug blocks SARS-CoV-2 transmission". medicalxpress.com. Retrieved 16 January 2021.
^ Cox RM, Wolf JD, Plemper RK (January 2021). "Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets". Nature Microbiology. 6 (1): 11–18. doi:10.1038/s41564-020-00835-2. PMC 7755744. PMID 33273742.
^ Covid antiviral pill can halve risk of hospitalisation BBC
^ Covid antiviral pill halves hospitalisations and deaths, maker says The Guardian
^ "Molnupiravir gets nod for emergency use in India: From how it works to countries who approved it, everything about antiviral pill". Financial Express. 29 December 2022. Retrieved 2 January 2022.
^ ^a ^b ^c Jeon, Sangeun; Ko, Meehyun; Lee, Jihye; Choi, Inhee; Byun, Soo Young; Park, Soonju; Shum, David; Kim, Seungtaek (4 May 2020). "Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs". Antimicrobial Agents and Chemotherapy. 64 (7). doi:10.1128/AAC.00819-20. PMC 7318052. PMID 32366720.
^ Morse JS, Lalonde T, Xu S, Liu WR (March 2020). "Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV". ChemBioChem. 21 (5): 730–38. doi:10.1002/cbic.202000047. PMC 7162020. PMID 32022370.
^ Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al. (March 2020). "Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases". ACS Central Science. 6 (3): 315–31. doi:10.1021/acscentsci.0c00272. PMC 7094090. PMID 32226821.
^ Ramajayam R, Tan KP, Liang PH (October 2011). "Recent development of 3C and 3CL protease inhibitors for anti-coronavirus and anti-picornavirus drug discovery". Biochemical Society Transactions. 39 (5): 1371–75. doi:10.1042/BST0391371. PMID 21936817.
^ Tao K, Tzou PL, Nouhin J, Bonilla H, Jagannathan P, Shafer RW (July 2021). "SARS-CoV-2 Antiviral Therapy". Clinical Microbiology Reviews. 34 (4): e0010921. doi:10.1128/CMR.00109-21. PMC 8404831. PMID 34319150. S2CID 236472654.
^ Simmons B, Wentzel H, Mobarak S, Eslami G, Sadeghi A, Ali Asgari A, et al. (January 2021). "Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis". The Journal of Antimicrobial Chemotherapy. 76 (2): 286–291. doi:10.1093/jac/dkaa418. PMC 7665526. PMID 33063117.
^ Zhang Y, Tang LV (January 2021). "Overview of Targets and Potential Drugs of SARS-CoV-2 According to the Viral Replication". J Proteome Res. 20 (1): 49–59. doi:10.1021/acs.jproteome.0c00526. ISSN 1535-3893. PMC 7770889. PMID 33347311.
^ Shrestha DB, Budhathoki P, Khadka S, Shah PB, Pokharel N, Rashmi P (September 2020). "Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis". Virol J. 17 (1): 141. doi:10.1186/s12985-020-01412-z. PMC 7512218. PMID 32972430.{{cite journal}}: CS1 maint: unflagged free DOI (link)
^ "Japanese flu drug 'clearly effective' in treating coronavirus, says China". 18 March 2020.
^ "Coronavirus: Japanese anti-viral drug effective in treating patients, Chinese official says". The Independent.
^ "Which Covid-19 drugs work best?". MIT Technology Review.
^ "Coronavirus, il Veneto sperimenta l'antivirale giapponese Favipiravir. Ma l'Aifa: "Ci sono scarse evidenze scientifiche su efficacia"". Il Fatto Quotidiano (in Italian). 22 March 2020. Retrieved 23 March 2020.
^ "AIFA precisa, uso favipiravir per COVID-19 non autorizzato in Europa e USA, scarse evidenze scientifiche sull'efficacia". aifa.gov.it (in Italian). Retrieved 23 March 2020.
^ "Russian Ministry of Health approves the first COVID-19 drug Avifavir produced by JV of RDIF and ChemRar". RDIF. 30 May 2020. Retrieved 31 May 2020.
^ "Russian Health Ministry approves anti-coronavirus drug Avifavir". BNN Bloomberg. 31 May 2020. Retrieved 31 May 2020.
^ "Russia plans coronavirus vaccine clinical trials in two weeks". Reuters. 30 May 2020. Retrieved 31 May 2020.
^ "Glenmark's FabiFlu approved for coronavirus treatment in India, costs Rs 103 per tablet". India Today. 20 June 2020. Retrieved 30 June 2020.
^ Swift R (18 February 2021). Feast L (ed.). "Fujifilm's Avigan shows no significant benefit on COVID-19 mortality: study". Reuters. Tokyo. Retrieved 25 April 2021.
^ Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, Martinez-de-Hoyo R (26 May 2021). "The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials". Scientific Reports. 11 (1): 11022. Bibcode:2021NatSR..1111022H. doi:10.1038/s41598-021-90551-6. ISSN 2045-2322. PMC 8155021. PMID 34040117.
^ Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. (March 2020). "Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors". Science. 368 (6489): 409–12. Bibcode:2020Sci...368..409Z. doi:10.1126/science.abb3405. PMC 7164518. PMID 32198291.
^ ^a ^b Kupferschmidt K, Cohen J (22 March 2020). "WHO launches global megatrial of the four most promising coronavirus treatments". Science Magazine. doi:10.1126/science.abb8497. S2CID 216325781. Retrieved 27 March 2020.
^ Mullard A (April 2020). "Flooded by the torrent: the COVID-19 drug pipeline". Lancet. 395 (10232): 1245–46. doi:10.1016/S0140-6736(20)30894-1. PMC 7162641. PMID 32305088.
^ ^a ^b Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. (March 2020). "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19". The New England Journal of Medicine. 382 (19): 1787–99. doi:10.1056/nejmoa2001282. PMC 7121492. PMID 32187464.
^ "Antiviral Drug Combo Ineffective Vs. Coronavirus". WebMD. 20 March 2020.
^ Brown J (20 March 2020). "Colorado researchers are racing to find an antiviral drug that could save people with the new coronavirus".
^ ^a ^b Devlin H, Sample I (19 March 2020). "What are the prospects for a COVID-19 treatment?". The Guardian.
^ "No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in Recovery" (PDF). Recovery Trial. 29 June 2020. Retrieved 30 June 2020.
^ Horby PW, Mafham M, Bell JL, Linsell L, Staplin N, Emberson J, Palfreeman A, Raw J, Elmahi E, Prudon B, Green C, et al. (Recovery Collaborative Group) (October 2020). "Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (Recovery): a randomised, controlled, open-label, platform trial". Lancet. 396 (10259): 1345–52. doi:10.1016/S0140-6736(20)32013-4. PMC 7535623. PMID 33031764. S2CID 222135901.
^ Bagheri M, Niavarani A (October 2020). "Molecular dynamics analysis predicts ritonavir and naloxegol strongly block the SARS-CoV-2 spike protein-hACE2 binding". Journal of Biomolecular Structure & Dynamics: 1–10. doi:10.1080/07391102.2020.1830854. PMID 33030105. S2CID 222217607.
^ ^a ^b ^c "Veklury EPAR". European Medicines Agency (EMA). 23 June 2020. Archived from the original on 18 March 2021. Retrieved 8 August 2022. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ "Gilead Announces Approval of Veklury (remdesivir) in Japan for Patients With Severe COVID-19" (Press release). Gilead Sciences. 7 May 2020. Archived from the original on 26 June 2020. Retrieved 25 June 2020 – via Business Wire.
^ Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A, Berrino L, Racagni G, Rossi F, Capuano A (April 2020). "Current pharmacological treatments for COVID-19: What's next?". British Journal of Pharmacology. 177 (21): 4813–4824. doi:10.1111/bph.15072. eISSN 1476-5381. PMC 7264618. PMID 32329520.
^ "Remdesivir". Drugs.com. 20 April 2020. Archived from the original on 16 April 2020. Retrieved 30 April 2020.
^ Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A (July 2020). "Pharmacotherapy in COVID-19; A narrative review for emergency providers". The American Journal of Emergency Medicine. 38 (7): 1488–1493. doi:10.1016/j.ajem.2020.04.035. eISSN 0735-6757. PMC 7158837. PMID 32336586.
^ "U.S. Food and Drug Administration Approves Gilead's Antiviral Veklury (remdesivir) for Treatment of COVID-19" (Press release). Gilead Sciences, Inc. 22 October 2020. Archived from the original on 23 October 2020. Retrieved 23 October 2020.
^ Stephens B (18 April 2020). "The Story of Remdesivir". The New York Times. p. A23. Archived from the original on 22 May 2020. Retrieved 11 May 2020.
^ Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N, Strickley R, Wells J, Stuthman KS, Van Tongeren SA, Garza NL, Donnelly G, Shurtleff AC, Retterer CJ, Gharaibeh D, Zamani R, Kenny T, Eaton BP, Grimes E, Welch LS, Gomba L, Wilhelmsen CL, Nichols DK, Nuss JE, Nagle ER, Kugelman JR, Palacios G, Doerffler E, Neville S, Carra E, Clarke MO, Zhang L, Lew W, Ross B, Wang Q, Chun K, Wolfe L, Babusis D, Park Y, Stray KM, Trancheva I, Feng JY, Barauskas O, Xu Y, Wong P, Braun MR, Flint M, McMullan LK, Chen SS, Fearns R, Swaminathan S, Mayers DL, Spiropoulou CF, Lee WA, Nichol ST, Cihlar T, Bavari S (March 2016). "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys". Nature. 531 (7594): 381–5. Bibcode:2016Natur.531..381W. doi:10.1038/nature17180. PMC 5551389. PMID 26934220.
^ Kupferschmidt K, Cohen J (22 March 2020). "WHO launches global megatrial of the four most promising coronavirus treatments". Science Magazine. doi:10.1126/science.abb8497. S2CID 216325781. Archived from the original on 14 September 2020. Retrieved 27 March 2020.
^ Yan VC, Muller FL (14 May 2020). "Gilead should ditch remdesivir and focus on its simpler and safer ancestor". Stat. Archived from the original on 12 June 2021. Retrieved 5 July 2020.
^ "FDA EUA Remdesivir Fact Sheet for Health Care Providers" (PDF). U.S. Food and Drug Administration (FDA). January 2022. Archived from the original on 24 January 2022. Retrieved 23 January 2022. This article incorporates text from this source, which is in the public domain.
^ "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021. This article incorporates text from this source, which is in the public domain.
^ "EMA starts evaluating the use of Kineret in adult COVID-19 patients at increased risk severe respiratory failure". European Medicines Agency (EMA) (Press release). 16 July 2021. Retrieved 20 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ ^a ^b "WHO officials enroll first patients from Norway and Spain in 'historic' coronavirus drug trial". CNBC. 27 March 2020.
^ ^a ^b "REMAP-CAP Trial". REMAP-CAP.
^ "Traumakine to be a part of WHO's Solidarity trial investigating potential COVID-19 treatments". Faron Pharmaceuticals (Press release). 27 April 2020. Retrieved 8 May 2020.
^ "Dexamethasone". The American Society of Health-System Pharmacists. Archived from the original on 31 August 2017. Retrieved 29 July 2015.
^ Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al. (March 2020). "Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial". The Lancet. Respiratory Medicine. 8 (3): 267–276. doi:10.1016/s2213-2600(19)30417-5. PMID 32043986. Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.
^ Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. (October 2020). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–41. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.
^ "Corticosteroids for COVID-19". Living Guidance. WHO. 2 September 2020. Retrieved 2 September 2020.
^ "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Retrieved 16 June 2020.
^ "Steroid drug hailed as 'breakthrough' for seriously ill COVID-19 patients". Reuters. 17 June 2020. Retrieved 18 June 2020.
^ Ducharme J. "A Low-Cost Steroid Shows Promise for Treating COVID-19. But Take the News With a Grain of Salt". Time. Retrieved 18 June 2020.
^ Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B (22 June 2020). Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report (Report). doi:10.1101/2020.06.22.20137273. S2CID 219965377.
^ Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. (February 2021). "Dexamethasone in Hospitalized Patients with Covid-19". The New England Journal of Medicine. 384 (8): 693–704. doi:10.1056/NEJMoa2021436. PMC 7383595. PMID 32678530.
^ "Corticosteroids (Including Dexamethasone)". COVID-19 Treatment Guidelines. National Institutes of Health. Retrieved 12 July 2020.
^ "Q&A: Dexamethasone and COVID-19". World Health Organization (WHO). Retrieved 12 July 2020.
^ ^a ^b "COVID-19 Guideline, Part 1: Treatment and Management". Infectious Diseases Society of America. Retrieved 22 July 2020. Recommendation 4. Among hospitalized patients with severe* COVID-19, the IDSA guideline panel suggests glucocorticoids rather than no glucocorticoids. (Conditional recommendation, Moderate certainty of evidence)
Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge if earlier) or equivalent glucocorticoid dose may be substituted if dexamethasone unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.
Recommendation 5. Among hospitalized patients with COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation, Low certainty of evidence)
^ "EMA starts review of dexamethasone for treating adults with COVID-19 requiring respiratory support". European Medicines Agency (EMA) (Press release). 24 July 2020. Retrieved 27 July 2020. Text was copied from this source, copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ ^a ^b ^c World Health Organization (2020). Corticosteroids for COVID-19: living guidance, 2 September 2020 (Report). World Health Organization (WHO). hdl:10665/334125. WHO/2019-nCoV/Corticosteroids/2020.1.
^ "WHO updates clinical care guidance with corticosteroid recommendations" (Press release). World Health Organization (WHO). Retrieved 23 January 2022.
^ ^a ^b "EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation". European Medicines Agency (EMA) (Press release). 18 September 2020. Retrieved 21 September 2020. Text was copied from this source, which is copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, et al. (October 2020). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–41. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.
^ "A parasitic infection that can turn fatal with administration of corticosteroids". WHO. 17 December 2021.
^ Ramakrishnan S, Nicolau DV, Langford B, Mahdi M, Jeffers H, Mwasuku C, Krassowska K, Fox R, Binnian I, Glover V, Bright S, Butler C, Cane JL, Halner A, Matthews PC, Donnelly LE, Simpson JL, Baker JR, Fadai NT, Peterson S, Bengtsson T, Barnes PJ, Russell RE, Bafadhel M (April 2021). "Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial". The Lancet. Respiratory Medicine. 9 (7): 763–772. doi:10.1016/S2213-2600(21)00160-0. PMC 8040526. PMID 33844996.
^ ^a ^b Agusti A, Torres F, Faner R (April 2021). "Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19". The Lancet. Respiratory Medicine (Commentary). 9 (7): 682–683. doi:10.1016/S2213-2600(21)00171-5. PMC 8040539. PMID 33844998.
^ "CAS-ViewAlert". www.cas.mhra.gov.uk. Retrieved 16 April 2021.
^ Deokar K, Agarwal M, Dutt N, Chauhan N, Niwas R, Shadrach BJ, Chawla G (2021). "A review of Ciclesonide in COVID-19. Still a long way to go". Advances in Respiratory Medicine. 89 (1): 79–81. doi:10.5603/ARM.a2020.0173. PMID 33471354.
^ ^a ^b Abobaker A, Alzwi A, Alraied AH (December 2020). "Overview of the possible role of vitamin C in management of COVID-19". Pharmacological Reports. 72 (6): 1517–28. doi:10.1007/s43440-020-00176-1. PMC 7592143. PMID 33113146.
^ "Search of: vitamin C | Recruiting, Completed Studies | COVID-19". clinicaltrials.gov. Retrieved 14 November 2021.
^ ^a ^b Rawat D, Roy A, Maitra S, Gulati A, Khanna P, Baidya DK (October 2021). "Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials". Diabetes & Metabolic Syndrome. 15 (6): 102324. doi:10.1016/j.dsx.2021.102324. PMC 8552785. PMID 34739908.
^ "Vitamin C". National Institutes of Health. This article incorporates text from this source, which is in the public domain.
^ ^a ^b ^c Martineau AR, Forouhi NG (September 2020). "Vitamin D for COVID-19: a case to answer?". The Lancet. Diabetes & Endocrinology. 8 (9): 735–6. doi:10.1016/S2213-8587(20)30268-0. PMC 7398646. PMID 32758429.
^ "Vitamin D". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 17 July 2020. Retrieved 22 February 2021. This article incorporates text from this source, which is in the public domain.
^ ^a ^b COVID-19 rapid guideline: vitamin D (PDF) (Technical report). National Institute for Health and Care Excellence (NICE). December 2020. ISBN 978-1-4731-3942-8. NG187. Retrieved 22 February 2021.
^ Damascena AD, Azevedo LM, Oliveira TA, Santana JD, Pereira M (August 2021). "Addendum to vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis". Critical Reviews in Food Science and Nutrition: 1–6. doi:10.1080/10408398.2021.1951652. ISSN 1549-7852. PMID 34384300. S2CID 236997712.
^ Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S (March 2021). "Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis". Advances in Nutrition. 12 (5): 1636–1658. doi:10.1093/advances/nmab012. PMC 7989595. PMID 33751020.
^ Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A (March 2021). "Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies". The Journal of Steroid Biochemistry and Molecular Biology. 211: 105883. doi:10.1016/j.jsbmb.2021.105883. PMC 7997262. PMID 33775818.
^ ^a ^b Bassatne A, Basbous M, Chakhtoura M, Zein OE, Rahme M, Fuleihan GE (March 2021). "The link between COVID-19 and Vitamin D (VIVID): a systematic review and meta-analysis". Metabolism (Systematic review). 119: 154753. doi:10.1016/j.metabol.2021.154753. PMC 7989070. PMID 33774074.
^ Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19 (PDF) (Report). National Institute for Health and Care Excellence (NICE). December 2020.
^ ^a ^b "International clinical trials assessing vitamin D in people with COVID-19". ClinicalTrials.gov. Retrieved 11 June 2021.
^ Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R (September 2020). "Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166". The Journal of Steroid Biochemistry and Molecular Biology. 202: 105719. doi:10.1016/j.jsbmb.2020.105719. PMC 7289092. PMID 32535032.
^ ^a ^b ^c ^d Shah K, Saxena D, Mavalankar D (January 2021). "Vitamin D supplementation, COVID-19 & Disease Severity: A meta-analysis". QJM: Monthly Journal of the Association of Physicians. 114 (3): 175–181. doi:10.1093/qjmed/hcab009. PMC 7928587. PMID 33486522.
^ Stroehlein JK, Wallqvist J, Iannizzi C, Mikolajewska A, Metzendorf MI, Benstoem C, et al. (May 2021). "Vitamin D supplementation for the treatment of COVID-19: a living systematic review". The Cochrane Database of Systematic Reviews. 2021 (5): CD015043. doi:10.1002/14651858.CD015043. PMC 8406457. PMID 34029377. S2CID 235202971.{{cite journal}}: CS1 maint: PMC embargo expired (link)
^ Cesareo R, Falchetti A, Attanasio R, Tabacco G, Naciu AM, Palermo A (May 2019). "Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?". Nutrients (Review). 11 (5): 1016. doi:10.3390/nu11051016. PMC 6566727. PMID 31064117.
^ "Zinc". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 21 April 2021. Retrieved 28 November 2021. This article incorporates text from this source, which is in the public domain.
^ Ansede M (3 April 2020). "Doscientos enfermos probarán un fármaco que ha bloqueado el coronavirus en minirriñones humanos". El País (in Spanish). Retrieved 3 April 2020.
^ "Apeiron Biologics moves forward with APN01 for treatment of COVID-19". www.thepharmaletter.com. Retrieved 3 April 2020.
^ "Coronavirus: Scientists could repurpose drugs to treat infection". Medical News Today. 28 February 2020. Retrieved 20 March 2020.
^ "Existing Drugs May Offer a First-Line Treatment for Coronavirus Outbreak". Global Health News Wire. Retrieved 20 March 2020.
^ Baron SA, Devaux C, Colson P, Raoult D, Rolain JM (April 2020). "Teicoplanin: an alternative drug for the treatment of COVID-19?". International Journal of Antimicrobial Agents. 55 (4): 105944. doi:10.1016/j.ijantimicag.2020.105944. PMC 7102624. PMID 32179150.
^ ^a ^b ^c Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, Oksenych V, Bjørås M, et al. (April 2020). "Discovery and development of safe-in-man broad-spectrum antiviral agents". International Journal of Infectious Diseases. 93: 268–276. doi:10.1016/j.ijid.2020.02.018. PMC 7128205. PMID 32081774.
^ ^a ^b "Amid Ongoing COVID-19 Pandemic, Governor Cuomo Accepts Recommendation of Army Corps of Engineers for Four Temporary Hospital Sites in New York". governor.ny.gov. 22 March 2020.
^ "Revive Therapeutics Announces U.S. FDA Approval of Confirmatory Phase 3 Clinical Trial for Bucillamine in COVID-19" (Press release). Revive Therapeutics Ltd. 31 July 2020. Retrieved 5 August 2020 – via GlobeNewswire.
^ Favalli EG, Biggioggero M, Maioli G, Caporali R (September 2020). "Baricitinib for COVID-19: a suitable treatment?". The Lancet. Infectious Diseases. 20 (9): 1012–13. doi:10.1016/S1473-3099(20)30262-0. ISSN 1473-3099. PMC 7270794. PMID 32251638.
^ "Coronavirus (COVID-19) Update: FDA Authorizes Drug Combination for Treatment of COVID-19" (Press release). FDA. 19 November 2020. Retrieved 4 December 2020.
^ "Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) of Baricitinib" (PDF). Indianapolis: Ely Lilly and Company. 19 November 2020. Retrieved 4 December 2020.
^ "EMA starts evaluating use of Olumiant in hospitalised COVID-19 patients requiring supplemental oxygen" (Press release). European Medicines Agency (EMA). 29 April 2021. Retrieved 29 April 2021.
^ "Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021.
^ "Fact Sheet for Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021.
^ ^a ^b "Coronavirus (COVID-19) Update: July 30, 2021". U.S. Food and Drug Administration (FDA) (Press release). 30 July 2021. Retrieved 30 July 2021. This article incorporates text from this source, which is in the public domain.
^ Firth A, Prathapan P (1 January 2021). "Broad-spectrum therapeutics: A new antimicrobial class". Current Research in Pharmacology and Drug Discovery. 2: 100011. doi:10.1016/j.crphar.2020.100011. PMC 8035643. PMID 34870144.
^ Firth A, Prathapan P (December 2020). "Azithromycin: The First Broad-spectrum Therapeutic". European Journal of Medicinal Chemistry. 207: 112739. doi:10.1016/j.ejmech.2020.112739. PMC 7434625. PMID 32871342.
^ "Biodefense Strategic Plan | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 2 February 2021.
^ "NIH funds development of new broad-spectrum therapeutics". National Institutes of Health (NIH). 18 September 2015. Retrieved 2 February 2021.
^ "New York clinical trial quietly tests heartburn remedy against coronavirus". Science. 26 April 2020.
^ ^a ^b "Début d'une étude clinique pour tester un médicament contre les effets de la COVID‑19 | Coronavirus". Radio-Canada.ca.
^ ^a ^b "COLCORONA Clinical Trial | Stop COVID-19". Colcorona.
^ Ehrlich A, Uhl S, Ioannidis K, Hofree M, tenOever BR, Nahmias Y (14 July 2020). "The SARS-CoV-2 Transcriptional Metabolic Signature in Lung Epithelium". SSRN 3650499.
^ "Antiviral Drug Reduces COVID-19 Inflammation In 48 Hours, Israeli Study Finds". 24 August 2021.
^ "Cholesterol Drug May Downgrade COVID-19 Threat - New Study". 29 July 2020.
^ "LIBERATE Trial in COVID-19 (LIBERATE)". ClinicalTrials.gov. Retrieved 10 September 2020.
^ "Coronavirus: Ibuprofen tested as a treatment". BBC News Online. 3 June 2020. Retrieved 4 June 2020.
^ Fink G, Orlova-Fink N, Schindler T, Grisi S, Ferrer AP, Daubenberger C, et al. (1 July 2020). "Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil (preprint)" (Document). doi:10.1101/2020.06.29.20142505. Covid-19 patients with recent influenza vaccination experience better health outcomes than non-vaccinated patients in Brazil. {{cite document}}: Cite document requires |publisher= (help); Unknown parameter |s2cid= ignored (help); Unknown parameter |work= ignored (help)
^ "Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma". ClinicalTrials.gov. 5 March 2020. Retrieved 10 September 2020.
^ Ning Q (14 March 2020). "A Pilot Study of Sildenafil in COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.

External links

"COVID-19 therapeutics tracker". Regulatory Affairs Professionals Society.
"STAT's Covid-19 Drugs and Vaccines Tracker". Stat. 27 April 2020.
"Coronavirus Drug and Treatment Tracker". The New York Times.
"JHMI Clinical Recommendations for Available Pharmacologic Therapies for COVID-19" (PDF). Johns Hopkins Medicine.
World Health Organization (2021). Therapeutics and COVID-19: living guideline, 24 September 2021 (Report). World Health Organization (WHO). hdl:10665/345356. WHO/2019-nCoV/therapeutics/2021.3.
Velasquez-Manoff M (11 August 2020). "How Covid Sends Some Bodies to War With Themselves". The New York Times.
Zimmer C (30 April 2020). "Old Drugs May Find a New Purpose: Fighting the Coronavirus". The New York Times.

[1] "Repurposing Drugs". National Center for Advancing Translational Sciences (NCATS). U.S. Department of Health & Human Services, National Institutes of Health. 7 November 2017. Retrieved 26 March 2020.

[Harrison_2020-2] Harrison C (April 2020). "Coronavirus puts drug repurposing on the fast track". Nature Biotechnology. 38 (4): 379–81. doi:10.1038/d41587-020-00003-1. PMID 32205870. S2CID 213394680.

[3] Sleigh SH, Barton CL (2010). "Repurposing Strategies for Therapeutics". Pharmaceutical Medicine. 24 (3): 151–59. doi:10.1007/BF03256811. S2CID 25267555.

[4] "COVID-19 Vaccine Frontrunners".

[5] Duan K, Liu B, Li C, Zhang H, Yu T, Qu J, et al. (April 2020). "Effectiveness of convalescent plasma therapy in severe COVID-19 patients". Proceedings of the National Academy of Sciences of the United States of America. 117 (17): 9490–96. doi:10.1073/pnas.2004168117. PMC 7196837. PMID 32253318.

[Li_2020-6] Li G, De Clercq E (March 2020). "Therapeutic options for the 2019 novel coronavirus (2019-nCoV)". Nature Reviews. Drug Discovery. 19 (3): 149–50. doi:10.1038/d41573-020-00016-0. PMID 32127666.

[milken-7] "COVID-19 treatment and vaccines tracker (Choose tab of interest, apply filters to view select data)". Milken Institute. 2 June 2020. Retrieved 3 June 2020.

[8] Sanders JM, Monogue ML, Jodlowski TZ, Cutrell JB (April 2020). "Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review". JAMA. 323 (18): 1824–36. doi:10.1001/jama.2020.6019. PMID 32282022.

[singhp:20-9] Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK (December 2020). "Drug repurposing approach to fight COVID-19". Pharmacological Reports. 72 (6): 1479–1508. doi:10.1007/s43440-020-00155-6. PMC 7474498. PMID 32889701.

[10] Zimmer C (30 January 2021). "How the Search for Covid-19 Treatments Faltered While Vaccines Sped Ahead". The New York Times.

[11] Kirtonia A, Gala K, Fernandes SG, Pandya G, Pandey AK, Sethi G, et al. (January 2021). "Repurposing of drugs: An attractive pharmacological strategy for cancer therapeutics". Seminars in Cancer Biology. 68: 258–78. doi:10.1016/j.semcancer.2020.04.006. ISSN 1044-579X. PMID 32380233. S2CID 218556384.

[12] Carbone M, Lednicky J, Xiao SY, Venditti M, Bucci E (April 2021). "Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For". Journal of Thoracic Oncology. 16 (4): 546–71. doi:10.1016/j.jtho.2020.12.014. PMC 7832772. PMID 33422679.

[RECOVERY_Home-13] "RECOVERY Trial". Retrieved 17 June 2020.

[14] "Anti-Interleukin-8 (Anti-IL-8) for Patients With COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.

[15] "Statement On A Nonproprietary Name Adopted By The USAN Council: Mavrilimumab" (PDF). American Medical Association. Archived from the original (PDF) on 28 September 2012.

[16] Burmester GR, Feist E, Sleeman MA, Wang B, White B, Magrini F (September 2011). "Mavrilimumab, a human monoclonal antibody targeting GM-CSF receptor-α, in subjects with rheumatoid arthritis: a randomised, double-blind, placebo-controlled, phase I, first-in-human study". Annals of the Rheumatic Diseases. 70 (9): 1542–49. doi:10.1136/ard.2010.146225. PMC 3147227. PMID 21613310.

[mavri-17] De Luca G, Cavalli G, Campochiaro C, Della-Torre E, Angelillo P, Tomelleri A, et al. (16 June 2020). "GM-CSF blockade with mavrilimumab in severe COVID-19 pneumonia and systemic hyperinflammation: a single-centre, prospective cohort study". The Lancet Rheumatology. 2 (8): e465–73. doi:10.1016/S2665-9913(20)30170-3. PMC 7430344. PMID 32835256.

[18] "Arthritis drugs effective in improving survival in sickest COVID-19 patients". National Institute for Health Research. 7 January 2021.

[Tocilizumab-NICE-19] "Product overview | COVID‑19 rapid evidence summary: Tocilizumab for COVID‑19 | Advice | NICE". Retrieved 20 January 2021.

[20] "WHO and Roche launch trials of potential coronavirus treatments". SwissInfo.Ch. 20 March 2020. Retrieved 8 August 2020.

[21] "Roche provides an update on the phase III COVACTA trial of Actemra/RoActemra in hospitalised patients with severe COVID-19 associated pneumonia". Roche (Press release). 29 July 2020. Retrieved 18 August 2020.

[pmid33933194-22] Gupta S, Leaf DE (May 2021). "Tocilizumab in COVID-19: some clarity amid controversy". Lancet. 397 (10285): 1599–1601. doi:10.1016/S0140-6736(21)00712-1. PMC 8084409. PMID 33933194.

[FDA_COVID_PR-23] "Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 24 June 2021. Retrieved 24 June 2021. This article incorporates text from this source, which is in the public domain.

[FDA_Tocilizumab_EUA-24] "Tocilizumab Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). June 2021. This article incorporates text from this source, which is in the public domain.

[FDA_EUA_FAQ-25] "Frequently Asked Questions on the Emergency Use Authorization for Actemra (tocilizumab) for Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). July 2021. This article incorporates text from this source, which is in the public domain.

[26] "EMA starts evaluating use of RoActemra in hospitalised adults with severe COVID-19". European Medicines Agency (EMA) (Press release). 16 August 2021. Retrieved 24 August 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[27] Tang N, Bai H, Chen X, Gong J, Li D, Sun Z (May 2020). "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy". Journal of Thrombosis and Haemostasis. 18 (5): 1094–9. doi:10.1111/jth.14817. PMID 32220112.

[28] "Medicines usable for treatment of COVID-19 disease". Italian Medicines Agency. Retrieved 29 March 2021.

[29] "Low molecular weight heparins in the treatment of adult patients with COVID-19". AIFA Italian Medicines Agencty. 24 November 2020.

[30] Weintraub A. "How COVID-19 could be crippled by an age-old blood thinner". Fierce Biotech. Retrieved 22 July 2020.

[31] "Coronavirus, al via studio su eparina per 300 pazienti". Adnkronos. Retrieved 15 April 2020.

[atspeed-32] Rogosnitzky M, Berkowitz E, Jadad AR (May 2020). "Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point". JMIR Public Health and Surveillance. 6 (2): e19199. doi:10.2196/19199. PMC 7224168. PMID 32374264.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[33] "Chinese Clinical Trial Register (ChiCTR) – The world health organization international clinical trials registered organization registered platform". www.chictr.org.cn.

[sciam-antidepressants-34] Landhuis E (12 November 2021). "Investigating Antidepressants' Surprising Effect on COVID Deaths". Scientific American. Retrieved 1 December 2021.

[35] Hoertel N, Sánchez-Rico M, Vernet R, Beeker N, Jannot A, Neuraz A, et al. (4 February 2021). "Association between antidepressant use and reduced risk of intubation or death in hospitalized patients with COVID-19: results from an observational study". Molecular Psychiatry. 26 (9): 5199–5212. doi:10.1038/s41380-021-01021-4. ISSN 1476-5578. PMID 33536545. S2CID 231794088.

[36] Sidik SM (October 2021). "Common antidepressant slashes risk of COVID death, study says". Nature. doi:10.1038/d41586-021-02988-4. PMID 34716441. S2CID 240229837.

[37] Fox, Maggie (28 October 2021). "Cheap, generic anti-depressant may reduce severe Covid-19 disease, study finds". CNN. Retrieved 22 November 2021.

[reis-38] Reis G, Dos Santos Moreira-Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, et al. (January 2022). "Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial". The Lancet. Global Health. 10 (1): e42–e51. doi:10.1016/S2214-109X(21)00448-4. PMC 8550952. PMID 34717820.

[39] Ontario COVID-19 Drugs and Biologics Clinical Practice Guidelines Working Group (23 December 2021). "Clinical Practice Guideline Summary: Recommended Drugs and Biologics in Adult Patients with COVID-19". Ontario COVID-19 Science Advisory Table. Version 6.0. doi:10.47326/ocsat.cpg.2021.6.0. S2CID 245441405.{{cite journal}}: CS1 maint: numeric names: authors list (link)

[pmid27036359-40] Zumla A, Rao M, Wallis RS, Kaufmann SH, Rustomjee R, Mwaba P, et al. (April 2016). "Host-directed therapies for infectious diseases: current status, recent progress, and future prospects". The Lancet. Infectious Diseases (review). 16 (4): e47–63. doi:10.1016/S1473-3099(16)00078-5. PMC 7164794. PMID 27036359.

[41] Sourimant J, Aggarwal M, Plemper RK (August 2021). "Progress and pitfalls of a year of drug repurposing screens against COVID-19". Current Opinion in Virology. 49: 183–193. doi:10.1016/j.coviro.2021.06.004. PMC 8214175. PMID 34218010.

[Wang_2020-42] Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. (March 2020). "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro". Cell Research. 30 (3): 269–271. doi:10.1038/s41422-020-0282-0. PMC 7054408. PMID 32020029.

[43] Gautret P, Lagier JC, Parola P, Hoang VT, Meddeb L, Mailhe M, et al. (March 2020). "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial". International Journal of Antimicrobial Agents. 56 (1): 105949. doi:10.1016/j.ijantimicag.2020.105949. PMC 7102549. PMID 32205204.

[44] Weston S, Coleman CM, Haupt R, Logue J, Matthews K, Li Y, et al. (October 2020). "Broad Anti-coronavirus Activity of Food and Drug Administration-Approved Drugs against SARS-CoV-2 In Vitro and SARS-CoV In Vivo". J Virol. 94 (21). doi:10.1128/JVI.01218-20. PMC 7565640. PMID 32817221.

[FBA-45] "ФМБА России: доказана противовирусная активность "Мефлохина" в отношении возбудителя COVID-19" (in Russian). Federal Biomedical Agency. 10 April 2020. Retrieved 11 April 2020.

[Caly2020-46] Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (April 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.

[47] "Atovaquone and Azithromycin Combination for Confirmed COVID-19 Infection". ClinicalTrials.gov. Retrieved 10 September 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_COVID-19_Treatment_Guidelines-48] "Chloroquine or Hydroxychloroquine". COVID-19 Treatment Guidelines. National Institutes of Health. Archived from the original on 28 August 2020. Retrieved 14 February 2021.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_FDA-2020-49] "Coronavirus (COVID-19) Update: Daily Roundup March 30, 2020". FDA. 30 March 2020. Archived from the original on 19 October 2020. Retrieved 28 February 2021.

[50] Smit M, Marinosci A, Agoritsas T, Calmy A (April 2021). "Prophylaxis for COVID-19: a systematic review". Clinical Microbiology and Infection (Systematic review). 27 (4): 532–537. doi:10.1016/j.cmi.2021.01.013. PMC 7813508. PMID 33476807.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_Meyerowitz2020-51] Meyerowitz EA, Vannier AG, Friesen MG, Schoenfeld S, Gelfand JA, Callahan MV, Kim AY, Reeves PM, Poznansky MC (May 2020). "Rethinking the role of hydroxychloroquine in the treatment of COVID-19". FASEB Journal. 34 (5): 6027–6037. doi:10.1096/fj.202000919. PMC 7267640. PMID 32350928.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_Juurlink2020-52] Juurlink DN (April 2020). "Safety considerations with chloroquine, hydroxychloroquine and azithromycin in the management of SARS-CoV-2 infection". CMAJ. 192 (17): E450–E453. doi:10.1503/cmaj.200528. PMC 7207200. PMID 32269021.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_ASHP2020COVID-53] "Assessment of Evidence for COVID-19-Related Treatments: Updated 4/3/2020". American Society of Health-System Pharmacists. Archived from the original on 14 April 2021. Retrieved 7 April 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_Yazdany2020-54] Yazdany J, Kim AH (June 2020). "Use of Hydroxychloroquine and Chloroquine During the COVID-19 Pandemic: What Every Clinician Should Know". Annals of Internal Medicine. 172 (11): 754–755. doi:10.7326/M20-1334. PMC 7138336. PMID 32232419.

[55] Singh, Bhagteshwar; Ryan, Hannah; Kredo, Tamara; Chaplin, Marty; Fletcher, Tom (12 February 2021). Cochrane Infectious Diseases Group (ed.). "Chloroquine or hydroxychloroquine for prevention and treatment of COVID-19". Cochrane Database of Systematic Reviews. 2021 (2): CD013587. doi:10.1002/14651858.CD013587.pub2. PMC 8094389. PMID 33624299.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_pmid38425958-56] Nag K, Tripura K, Datta A, Karmakar N, Singh M, Singh M, Singal K, Pradhan P (2024). "Effect of Hydroxychloroquine and Azithromycin Combination Use in COVID-19 Patients - An Umbrella Review". Indian J Community Med. 49 (1): 22–27. doi:10.4103/ijcm.ijcm_983_22. PMC 10900474. PMID 38425958.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_hrthm-57] Jankelson L, Karam G, Becker ML, Chinitz LA, Tsai M (2020). "QT prolongation, torsades de pointes, and sudden death with short courses of chloroquine or hydroxychloroquine as used in COVID-19: A systematic review". Heart Rhythm. 17 (9): 1472–1479. doi:10.1016/j.hrthm.2020.05.008. PMC 7211688. PMID 32438018.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_deaths_induced-58] Pradelle, Alexiane; Mainbourg, Sabine; Provencher, Steeve; Massy, Emmanuel; Grenet, Guillaume; Lega, Jean-Christophe (February 2024). "Deaths induced by compassionate use of hydroxychloroquine during the first COVID-19 wave: an estimate". Biomedicine & Pharmacotherapy. 171. doi:10.1016/j.biopha.2023.116055. PMID 38171239. S2CID 266754199.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_pmid34611326-59] Jackson CB, Farzan M, Chen B, Choe H (January 2022). "Mechanisms of SARS-CoV-2 entry into cells". Nature Reviews. Molecular Cell Biology. 23 (1): 3–20. doi:10.1038/s41580-021-00418-x. PMC 8491763. PMID 34611326.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_cdc3-212-60] "Information for clinicians on therapeutic options for COVID-19 patients". US Centers for Disease Control and Prevention. 21 March 2020. Archived from the original on 8 April 2020. Retrieved 22 March 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_hinton2-61] Hinton DM (28 March 2020). "Request for Emergency Use Authorization For Use of Chloroquine Phosphate or Hydroxychloroquine Sulfate Supplied From the Strategic National Stockpile for Treatment of 2019 Coronavirus Disease" (PDF). U.S. Food and Drug Administration (FDA). Archived from the original on 2 October 2020. Retrieved 30 March 2020.

[62] "Coronavirus Disease 2019 (COVID-19)". Centers for Disease Control and Prevention. 11 February 2020. Archived from the original on 8 April 2020. Retrieved 9 April 2020.

[63] Kalil AC (May 2020). "Treating COVID-19-Off-Label Drug Use, Compassionate Use, and Randomized Clinical Trials During Pandemics". JAMA. 323 (19): 1897–1898. doi:10.1001/jama.2020.4742. PMID 32208486.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_fda.gov-64] "FDA cautions against use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to risk of heart rhythm problems". U.S. Food and Drug Administration (FDA). 24 April 2020. Archived from the original on 4 November 2020. Retrieved 28 February 2021.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_mulier2-65] Mulier T (17 June 2020). "Hydroxychloroquine halted in WHO-sponsored COVID-19 trials". Bloomberg. Archived from the original on 11 October 2020. Retrieved 17 June 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_rec-nobenefit3-66] "No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19". Recovery Trial, Nuffield Department of Population Health, University of Oxford, UK. 5 June 2020. Archived from the original on 8 October 2020. Retrieved 7 June 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_HCQ_and_CQ_revocation_PR2-67] "Coronavirus (COVID-19) Update: FDA Revokes Emergency Use Authorization for Chloroquine and Hydroxychloroquine". U.S. Food and Drug Administration (FDA) (Press release). 15 June 2020. Archived from the original on 15 June 2020. Retrieved 15 June 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_Lovelace_Jr-2020-68] Lovelace Jr B (15 June 2020). "FDA revokes emergency use of hydroxychloroquine". CNBC. Archived from the original on 11 October 2020. Retrieved 28 February 2021.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_HCQ_and_CQ_EUA_revocation_FAQ2-69] "Frequently Asked Questions on the Revocation of the Emergency Use Authorization for Hydroxychloroquine Sulfate and Chloroquine Phosphate" (PDF). U.S. Food and Drug Administration (FDA). 15 June 2020. Archived from the original on 15 April 2021. Retrieved 15 June 2020.

[Chloroquine_and_hydroxychloroquine_during_the_COVID-19_pandemic_HCQIndia-70] "Clinical Management Protocol for Covid-19 (in Adults)" (PDF). Ministry of Health and Family Welfare. 24 May 2021. Archived (PDF) from the original on 5 December 2021. Retrieved 10 July 2021. "Health ministry issues revised clinical management protocols for Covid-19 amid spurt in cases". Times of India. Press Trust of India. 13 June 2021. Archived from the original on 11 July 2021. Retrieved 10 July 2021.

[Ivermectin_during_the_COVID-19_pandemic_Ramadan2021-71] Tafoya QJ (2021). "Appendix – COVID-19-Directed Medications". In Ramadan AR, Gamaleldin O (eds.). Neurological Care and the COVID-19 Pandemic (1st ed.). Elsevier. pp. 173–174. doi:10.1016/B978-0-323-82691-4.00016-9. ISBN 978-0-323-82691-4. S2CID 239763031. The WHO, the European Medicines Agency, and the IDSA all recommend against the use of ivermectin for treatment of COVID-19, with the NIH stating that there is insufficient data to recommend for or against its use outside the context of a clinical trial.

[Ivermectin_during_the_COVID-19_pandemic_WHO2021-72] "WHO advises that ivermectin only be used to treat COVID-19 within clinical trials". Newsroom. World Health Organization. Geneva, Switzerland. 31 March 2021. Retrieved 12 May 2023.

[Ivermectin_during_the_COVID-19_pandemic_EMA2021-73] "EMA advises against use of ivermectin for the prevention or treatment of COVID-19 outside randomised clinical trials". News. European Medicines Agency. Amsterdam. 22 March 2021. Retrieved 12 May 2023.

[Ivermectin_during_the_COVID-19_pandemic_USFDA2021-74] "Why You Should Not Use Ivermectin to Treat or Prevent COVID-19". United States Food and Drug Administration. Consumer Updates. Silver Spring, Maryland: Food and Drug Administration. 10 December 2021. Retrieved 12 May 2023.

[Ivermectin_during_the_COVID-19_pandemic_IDSA2023-75] "IDSA Guidelines on the Treatment and Management of Patients with COVID-19: Recommendations 23-24: Ivermectin". Infectious Diseases Society of America. IDSA Practice Guidelines. Arlington, Virginia. 11 April 2023. Retrieved 12 May 2023.

[Ivermectin_during_the_COVID-19_pandemic_Caly2020-76] Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM (June 2020). "The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro". Antiviral Research. 178: 104787. doi:10.1016/j.antiviral.2020.104787. PMC 7129059. PMID 32251768.

[Ivermectin_during_the_COVID-19_pandemic_shortage-77] Woo E (28 September 2021). "How Covid Misinformation Created a Run on Animal Medicine". New York Times. Archived from the original on 7 January 2022. Retrieved 23 December 2021.

[Ivermectin_during_the_COVID-19_pandemic_langford-78] Langford C (1 September 2023). "Fifth Circuit sides with ivermectin-prescribing doctors in their quarrel with the FDA". Courthouse News Service.

[Ivermectin_during_the_COVID-19_pandemic_coch2022-79] Popp M, Reis S, Schießer S, Hausinger RI, Stegemann M, Metzendorf MI, Kranke P, Meybohm P, Skoetz N, Weibel S (June 2022). "Ivermectin for preventing and treating COVID-19". Cochrane Database Syst Rev (Systematic review). 2022 (6): CD015017. doi:10.1002/14651858.CD015017.pub3. PMC 9215332. PMID 35726131.

[80] Reis G, Silva EA, Silva DC, Thabane L, Milagres AC, Ferreira TS, Dos Santos CV, Campos VH, Nogueira AM, de Almeida AP, Callegari ED, Neto AD, Savassi LC, Simplicio MI, Ribeiro LB, Oliveira R, Harari O, Forrest JI, Ruton H, Sprague S, McKay P, Guo CM, Rowland-Yeo K, Guyatt GH, Boulware DR, Rayner CR, Mills EJ (May 2022). "Effect of Early Treatment with Ivermectin among Patients with Covid-19". N Engl J Med (Randomized controlled trial). 386 (18): 1721–1731. doi:10.1056/NEJMoa2115869. PMC 9006771. PMID 35353979.

[81] Lawrence JM, Meyerowitz-Katz G, Heathers JA, Brown NJ, Sheldrick KA (November 2021). "The lesson of ivermectin: meta-analyses based on summary data alone are inherently unreliable". Nature Medicine. 27 (11): 1853–1854. doi:10.1038/s41591-021-01535-y. PMID 34552263. S2CID 237607620.

[82] "Ivermectin: How false science created a Covid 'miracle' drug". BBC News. 6 October 2021. Archived from the original on 8 January 2022. Retrieved 26 December 2021.

[Ivermectin_during_the_COVID-19_pandemic_Guardian2021-83] Melissa Davey (15 July 2021). "Huge study supporting ivermectin as Covid treatment withdrawn over ethical concerns". The Guardian. Archived from the original on 16 January 2022. Retrieved 12 May 2023.

[Dong_2020-84] Dong L, Hu S, Gao J (2020). "Discovering drugs to treat coronavirus disease 2019 (COVID-19)". Drug Discoveries & Therapeutics. 14 (1): 58–60. doi:10.5582/ddt.2020.01012. PMID 32147628.

[wang-85] Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. (May 2020). "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial". Lancet. 395 (10236): 1569–78. doi:10.1016/S0140-6736(20)31022-9. PMC 7190303. PMID 32423584.

[86] Lu CC, Chen MY, Lee WS, Chang YL (2020). "Potential therapeutic agents against COVID-19: What we know so far". J Chin Med Assoc. 83 (6): 534–36. doi:10.1097/JCMA.0000000000000318. PMC 7176266. PMID 32243270.

[87] Wu X, Yu K, Wang Y, Xu W, Ma H, Hou Y, et al. (July 2020). "The Efficacy and Safety of Triazavirin for COVID-19: A Trial Protocol". Engineering (Beijing). 6 (10): 1199–204. doi:10.1016/j.eng.2020.06.011. PMC 7332434. PMID 32837750.

[88] Lu H (March 2020). "Drug treatment options for the 2019-new coronavirus (2019-nCoV)". Bioscience Trends. 14 (1): 69–71. doi:10.5582/bst.2020.01020. PMID 31996494.

[89] "'Pyramax' drug repurposing?... targets COVID-19 treatment". Doctor's News. Retrieved 25 June 2020.

[90] Bae JY, Lee GE, Park H, Cho J, Kim YE, Lee JY, et al. (2020). "Pyronaridine and artesunate are potential antiviral drugs against COVID-19 and influenza". bioRxiv. doi:10.1101/2020.07.28.225102. S2CID 220885187.

[91] "COVID-19: Pyramax Enters Phase II Clinical Trial in South Korea". www.pharmanewsonline.com. Retrieved 17 June 2020.

[92] "A Multi-center, Randomized, Double-blind, Parallel, Placebo-Controlled, Phase II Clinical Trial to Evaluate Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". nedrug.mfds.go.kr. Retrieved 25 June 2020.

[93] "The Efficacy and Safety of Pyramax in Mild to Moderate COVID-19 Patients". ClinicalTrials.gov. Retrieved 10 September 2020.

[94] "COVID-19 Treatment in South Africa". ClinicalTrials.gov. Retrieved 21 September 2020.

[95] Zhang S (8 May 2020). "A Much-Hyped COVID-19 Drug Is Almost Identical to a Black-Market Cat Cure". The Atlantic.

[96] Pedersen NC, Perron M, Bannasch M, Montgomery E, Murakami E, Liepnieks M, et al. (April 2019). "Efficacy and safety of the nucleoside analog GS-441524 for treatment of cats with naturally occurring feline infectious peritonitis". Journal of Feline Medicine and Surgery. 21 (4): 271–81. doi:10.1177/1098612X19825701. PMC 6435921. PMID 30755068.

[Yan20-97] Yan VC, Muller FL (July 2020). "Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment". ACS Medicinal Chemistry Letters. 11 (7): 1361–66. doi:10.1021/acsmedchemlett.0c00316. PMC 7315846. PMID 32665809.

[pmid26934220-98] Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, et al. (March 2016). "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys". Nature. 531 (7594): 381–85. Bibcode:2016Natur.531..381W. doi:10.1038/nature17180. PMC 5551389. PMID 26934220.

[99] Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, et al. (June 2017). "Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses". Science Translational Medicine. 9 (396): eaal3653. doi:10.1126/scitranslmed.aal3653. PMC 5567817. PMID 28659436.

[100] Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. (April 2020). "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2". bioRxiv: 2020.04.15.043166. doi:10.1101/2020.04.15.043166. PMC 7239049. PMID 32511319.

[101] "Gilead should ditch remdesivir and focus on its simpler ancestor". Stat. 14 May 2020. Retrieved 5 June 2020.

[102] Yan VC, Muller FL (14 May 2020). "Gilead should ditch remdesivir and focus on its simpler and safer ancestor". Statnews.

[103] Westgate J (7 May 2020). "Vet science 'being ignored' in quest for COVID-19 drug". Vet Times. Retrieved 28 July 2020.

[104] Avoxa-Mediengruppe Deutscher Apotheker GmbH. "Verwandtschaft ersten Grades: Remdesivir-Metabolit noch schärfere Waffe gegen Covid-19?". Pharmazeutische Zeitung online (in German).

[105] "Study of MK-4482 for Prevention of Coronavirus Disease 2019 (COVID-19) in Adults (MK-4482-013)". ClinicalTrials.gov. 25 June 2021. Retrieved 18 October 2021.

[106] "Efficacy and Safety of Molnupiravir (MK-4482) in Hospitalized Adult Participants With COVID-19 (MK-4482-001)". ClinicalTrials.gov. 5 October 2020. Retrieved 18 October 2021.

[107] "Efficacy and Safety of Molnupiravir (MK-4482) in Non-Hospitalized Adult Participants With COVID-19 (MK-4482-002)". ClinicalTrials.gov. 5 October 2020. Retrieved 18 October 2021.

[108] "A Safety, Tolerability and Efficacy of EIDD-2801 to Eliminate Infectious Virus Detection in Persons With COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.

[109] "The Safety of EIDD-2801 and Its Effect on Viral Shedding of SARS-CoV-2 (END-COVID)". ClinicalTrials.gov. Retrieved 10 September 2020.

[110] "Oral drug blocks SARS-CoV-2 transmission". medicalxpress.com. Retrieved 16 January 2021.

[111] Cox RM, Wolf JD, Plemper RK (January 2021). "Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets". Nature Microbiology. 6 (1): 11–18. doi:10.1038/s41564-020-00835-2. PMC 7755744. PMID 33273742.

[112] Covid antiviral pill can halve risk of hospitalisation BBC

[113] Covid antiviral pill halves hospitalisations and deaths, maker says The Guardian

[MolnupiravarApprovals-114] "Molnupiravir gets nod for emergency use in India: From how it works to countries who approved it, everything about antiviral pill". Financial Express. 29 December 2022. Retrieved 2 January 2022.

[doi_10.1128/aac.00819-20-115] Jeon, Sangeun; Ko, Meehyun; Lee, Jihye; Choi, Inhee; Byun, Soo Young; Park, Soonju; Shum, David; Kim, Seungtaek (4 May 2020). "Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs". Antimicrobial Agents and Chemotherapy. 64 (7). doi:10.1128/AAC.00819-20. PMC 7318052. PMID 32366720.

[116] Morse JS, Lalonde T, Xu S, Liu WR (March 2020). "Learning from the Past: Possible Urgent Prevention and Treatment Options for Severe Acute Respiratory Infections Caused by 2019-nCoV". ChemBioChem. 21 (5): 730–38. doi:10.1002/cbic.202000047. PMC 7162020. PMID 32022370.

[117] Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, et al. (March 2020). "Research and Development on Therapeutic Agents and Vaccines for COVID-19 and Related Human Coronavirus Diseases". ACS Central Science. 6 (3): 315–31. doi:10.1021/acscentsci.0c00272. PMC 7094090. PMID 32226821.

[118] Ramajayam R, Tan KP, Liang PH (October 2011). "Recent development of 3C and 3CL protease inhibitors for anti-coronavirus and anti-picornavirus drug discovery". Biochemical Society Transactions. 39 (5): 1371–75. doi:10.1042/BST0391371. PMID 21936817.

[119] Tao K, Tzou PL, Nouhin J, Bonilla H, Jagannathan P, Shafer RW (July 2021). "SARS-CoV-2 Antiviral Therapy". Clinical Microbiology Reviews. 34 (4): e0010921. doi:10.1128/CMR.00109-21. PMC 8404831. PMID 34319150. S2CID 236472654.

[120] Simmons B, Wentzel H, Mobarak S, Eslami G, Sadeghi A, Ali Asgari A, et al. (January 2021). "Sofosbuvir/daclatasvir regimens for the treatment of COVID-19: an individual patient data meta-analysis". The Journal of Antimicrobial Chemotherapy. 76 (2): 286–291. doi:10.1093/jac/dkaa418. PMC 7665526. PMID 33063117.

[121] Zhang Y, Tang LV (January 2021). "Overview of Targets and Potential Drugs of SARS-CoV-2 According to the Viral Replication". J Proteome Res. 20 (1): 49–59. doi:10.1021/acs.jproteome.0c00526. ISSN 1535-3893. PMC 7770889. PMID 33347311.

[122] Shrestha DB, Budhathoki P, Khadka S, Shah PB, Pokharel N, Rashmi P (September 2020). "Favipiravir versus other antiviral or standard of care for COVID-19 treatment: a rapid systematic review and meta-analysis". Virol J. 17 (1): 141. doi:10.1186/s12985-020-01412-z. PMC 7512218. PMID 32972430.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[123] "Japanese flu drug 'clearly effective' in treating coronavirus, says China". 18 March 2020.

[ind-124] "Coronavirus: Japanese anti-viral drug effective in treating patients, Chinese official says". The Independent.

[125] "Which Covid-19 drugs work best?". MIT Technology Review.

[126] "Coronavirus, il Veneto sperimenta l'antivirale giapponese Favipiravir. Ma l'Aifa: "Ci sono scarse evidenze scientifiche su efficacia"". Il Fatto Quotidiano (in Italian). 22 March 2020. Retrieved 23 March 2020.

[127] "AIFA precisa, uso favipiravir per COVID-19 non autorizzato in Europa e USA, scarse evidenze scientifiche sull'efficacia". aifa.gov.it (in Italian). Retrieved 23 March 2020.

[128] "Russian Ministry of Health approves the first COVID-19 drug Avifavir produced by JV of RDIF and ChemRar". RDIF. 30 May 2020. Retrieved 31 May 2020.

[129] "Russian Health Ministry approves anti-coronavirus drug Avifavir". BNN Bloomberg. 31 May 2020. Retrieved 31 May 2020.

[130] "Russia plans coronavirus vaccine clinical trials in two weeks". Reuters. 30 May 2020. Retrieved 31 May 2020.

[131] "Glenmark's FabiFlu approved for coronavirus treatment in India, costs Rs 103 per tablet". India Today. 20 June 2020. Retrieved 30 June 2020.

[132] Swift R (18 February 2021). Feast L (ed.). "Fujifilm's Avigan shows no significant benefit on COVID-19 mortality: study". Reuters. Tokyo. Retrieved 25 April 2021.

[133] Hassanipour S, Arab-Zozani M, Amani B, Heidarzad F, Fathalipour M, Martinez-de-Hoyo R (26 May 2021). "The efficacy and safety of Favipiravir in treatment of COVID-19: a systematic review and meta-analysis of clinical trials". Scientific Reports. 11 (1): 11022. Bibcode:2021NatSR..1111022H. doi:10.1038/s41598-021-90551-6. ISSN 2045-2322. PMC 8155021. PMID 34040117.

[zhanglin-134] Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. (March 2020). "Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors". Science. 368 (6489): 409–12. Bibcode:2020Sci...368..409Z. doi:10.1126/science.abb3405. PMC 7164518. PMID 32198291.

[kai2-135] Kupferschmidt K, Cohen J (22 March 2020). "WHO launches global megatrial of the four most promising coronavirus treatments". Science Magazine. doi:10.1126/science.abb8497. S2CID 216325781. Retrieved 27 March 2020.

[Mullard_2020-136] Mullard A (April 2020). "Flooded by the torrent: the COVID-19 drug pipeline". Lancet. 395 (10232): 1245–46. doi:10.1016/S0140-6736(20)30894-1. PMC 7162641. PMID 32305088.

[Cao-137] Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. (March 2020). "A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19". The New England Journal of Medicine. 382 (19): 1787–99. doi:10.1056/nejmoa2001282. PMC 7121492. PMID 32187464.

[138] "Antiviral Drug Combo Ineffective Vs. Coronavirus". WebMD. 20 March 2020.

[Colorado_Sun-139] Brown J (20 March 2020). "Colorado researchers are racing to find an antiviral drug that could save people with the new coronavirus".

[guardian-140] Devlin H, Sample I (19 March 2020). "What are the prospects for a COVID-19 treatment?". The Guardian.

[lop-rit-141] "No clinical benefit from use of lopinavir-ritonavir in hospitalised COVID-19 patients studied in Recovery" (PDF). Recovery Trial. 29 June 2020. Retrieved 30 June 2020.

[reclop-142] Horby PW, Mafham M, Bell JL, Linsell L, Staplin N, Emberson J, Palfreeman A, Raw J, Elmahi E, Prudon B, Green C, et al. (Recovery Collaborative Group) (October 2020). "Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (Recovery): a randomised, controlled, open-label, platform trial". Lancet. 396 (10259): 1345–52. doi:10.1016/S0140-6736(20)32013-4. PMC 7535623. PMID 33031764. S2CID 222135901.

[143] Bagheri M, Niavarani A (October 2020). "Molecular dynamics analysis predicts ritonavir and naloxegol strongly block the SARS-CoV-2 spike protein-hACE2 binding". Journal of Biomolecular Structure & Dynamics: 1–10. doi:10.1080/07391102.2020.1830854. PMID 33030105. S2CID 222217607.

[Remdesivir_Veklury_EPAR-144] "Veklury EPAR". European Medicines Agency (EMA). 23 June 2020. Archived from the original on 18 March 2021. Retrieved 8 August 2022. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[Remdesivir_Gilead_PR-145] "Gilead Announces Approval of Veklury (remdesivir) in Japan for Patients With Severe COVID-19" (Press release). Gilead Sciences. 7 May 2020. Archived from the original on 26 June 2020. Retrieved 25 June 2020 – via Business Wire.

[Remdesivir_Scavone_2020-146] Scavone C, Brusco S, Bertini M, Sportiello L, Rafaniello C, Zoccoli A, Berrino L, Racagni G, Rossi F, Capuano A (April 2020). "Current pharmacological treatments for COVID-19: What's next?". British Journal of Pharmacology. 177 (21): 4813–4824. doi:10.1111/bph.15072. eISSN 1476-5381. PMC 7264618. PMID 32329520.

[147] "Remdesivir". Drugs.com. 20 April 2020. Archived from the original on 16 April 2020. Retrieved 30 April 2020.

[Remdesivir_Mehta2020-148] Mehta N, Mazer-Amirshahi M, Alkindi N, Pourmand A (July 2020). "Pharmacotherapy in COVID-19; A narrative review for emergency providers". The American Journal of Emergency Medicine. 38 (7): 1488–1493. doi:10.1016/j.ajem.2020.04.035. eISSN 0735-6757. PMC 7158837. PMID 32336586.

[Remdesivir_Gilead_PR_20201022-149] "U.S. Food and Drug Administration Approves Gilead's Antiviral Veklury (remdesivir) for Treatment of COVID-19" (Press release). Gilead Sciences, Inc. 22 October 2020. Archived from the original on 23 October 2020. Retrieved 23 October 2020.

[Remdesivir_Stephens2-150] Stephens B (18 April 2020). "The Story of Remdesivir". The New York Times. p. A23. Archived from the original on 22 May 2020. Retrieved 11 May 2020.

[Remdesivir_pmid269342202-151] Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N, Strickley R, Wells J, Stuthman KS, Van Tongeren SA, Garza NL, Donnelly G, Shurtleff AC, Retterer CJ, Gharaibeh D, Zamani R, Kenny T, Eaton BP, Grimes E, Welch LS, Gomba L, Wilhelmsen CL, Nichols DK, Nuss JE, Nagle ER, Kugelman JR, Palacios G, Doerffler E, Neville S, Carra E, Clarke MO, Zhang L, Lew W, Ross B, Wang Q, Chun K, Wolfe L, Babusis D, Park Y, Stray KM, Trancheva I, Feng JY, Barauskas O, Xu Y, Wong P, Braun MR, Flint M, McMullan LK, Chen SS, Fearns R, Swaminathan S, Mayers DL, Spiropoulou CF, Lee WA, Nichol ST, Cihlar T, Bavari S (March 2016). "Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys". Nature. 531 (7594): 381–5. Bibcode:2016Natur.531..381W. doi:10.1038/nature17180. PMC 5551389. PMID 26934220.

[Remdesivir_kai2-152] Kupferschmidt K, Cohen J (22 March 2020). "WHO launches global megatrial of the four most promising coronavirus treatments". Science Magazine. doi:10.1126/science.abb8497. S2CID 216325781. Archived from the original on 14 September 2020. Retrieved 27 March 2020.

[Remdesivir_Yan_2020-153] Yan VC, Muller FL (14 May 2020). "Gilead should ditch remdesivir and focus on its simpler and safer ancestor". Stat. Archived from the original on 12 June 2021. Retrieved 5 July 2020.

[Remdesivir_FDA_Remdesivir_EUA_Fact_Sheet-154] "FDA EUA Remdesivir Fact Sheet for Health Care Providers" (PDF). U.S. Food and Drug Administration (FDA). January 2022. Archived from the original on 24 January 2022. Retrieved 23 January 2022. This article incorporates text from this source, which is in the public domain.

[155] "New Drug Therapy Approvals 2020". U.S. Food and Drug Administration (FDA). 31 December 2020. Archived from the original on 18 January 2021. Retrieved 17 January 2021. This article incorporates text from this source, which is in the public domain.

[156] "EMA starts evaluating the use of Kineret in adult COVID-19 patients at increased risk severe respiratory failure". European Medicines Agency (EMA) (Press release). 16 July 2021. Retrieved 20 July 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[beta1-157] "WHO officials enroll first patients from Norway and Spain in 'historic' coronavirus drug trial". CNBC. 27 March 2020.

[beta2-158] "REMAP-CAP Trial". REMAP-CAP.

[159] "Traumakine to be a part of WHO's Solidarity trial investigating potential COVID-19 treatments". Faron Pharmaceuticals (Press release). 27 April 2020. Retrieved 8 May 2020.

[AHFS2015-160] "Dexamethasone". The American Society of Health-System Pharmacists. Archived from the original on 31 August 2017. Retrieved 29 July 2015.

[161] Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, et al. (March 2020). "Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial". The Lancet. Respiratory Medicine. 8 (3): 267–276. doi:10.1016/s2213-2600(19)30417-5. PMID 32043986. Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.

[SterneMurthyDiaz2020-162] Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, et al. (October 2020). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–41. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.

[163] "Corticosteroids for COVID-19". Living Guidance. WHO. 2 September 2020. Retrieved 2 September 2020.

[oxford_news-164] "Dexamethasone reduces death in hospitalised patients with severe respiratory complications of COVID-19". University of Oxford. 16 June 2020. Retrieved 16 June 2020.

[Reuters_16Jun20-165] "Steroid drug hailed as 'breakthrough' for seriously ill COVID-19 patients". Reuters. 17 June 2020. Retrieved 18 June 2020.

[Time_2020-06-16-166] Ducharme J. "A Low-Cost Steroid Shows Promise for Treating COVID-19. But Take the News With a Grain of Salt". Time. Retrieved 18 June 2020.

[167] Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B (22 June 2020). Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report (Report). doi:10.1101/2020.06.22.20137273. S2CID 219965377.

[168] Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, et al. (February 2021). "Dexamethasone in Hospitalized Patients with Covid-19". The New England Journal of Medicine. 384 (8): 693–704. doi:10.1056/NEJMoa2021436. PMC 7383595. PMID 32678530.

[169] "Corticosteroids (Including Dexamethasone)". COVID-19 Treatment Guidelines. National Institutes of Health. Retrieved 12 July 2020.

[170] "Q&A: Dexamethasone and COVID-19". World Health Organization (WHO). Retrieved 12 July 2020.

[IDSA-171] "COVID-19 Guideline, Part 1: Treatment and Management". Infectious Diseases Society of America. Retrieved 22 July 2020. Recommendation 4. Among hospitalized patients with severe* COVID-19, the IDSA guideline panel suggests glucocorticoids rather than no glucocorticoids. (Conditional recommendation, Moderate certainty of evidence)
Remark: Dexamethasone 6 mg IV or PO for 10 days (or until discharge if earlier) or equivalent glucocorticoid dose may be substituted if dexamethasone unavailable. Equivalent total daily doses of alternative glucocorticoids to dexamethasone 6 mg daily are methylprednisolone 32 mg and prednisone 40 mg.
Recommendation 5. Among hospitalized patients with COVID-19 without hypoxemia requiring supplemental oxygen, the IDSA guideline panel suggests against the use of glucocorticoids. (Conditional recommendation, Low certainty of evidence)

[EMA_review-172] "EMA starts review of dexamethasone for treating adults with COVID-19 requiring respiratory support". European Medicines Agency (EMA) (Press release). 24 July 2020. Retrieved 27 July 2020. Text was copied from this source, copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[WHO_guidance-173] World Health Organization (2020). Corticosteroids for COVID-19: living guidance, 2 September 2020 (Report). World Health Organization (WHO). hdl:10665/334125. WHO/2019-nCoV/Corticosteroids/2020.1.

[174] "WHO updates clinical care guidance with corticosteroid recommendations" (Press release). World Health Organization (WHO). Retrieved 23 January 2022.

[EMA_PR-175] "EMA endorses use of dexamethasone in COVID-19 patients on oxygen or mechanical ventilation". European Medicines Agency (EMA) (Press release). 18 September 2020. Retrieved 21 September 2020. Text was copied from this source, which is copyrighted by the European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

[176] Sterne JA, Murthy S, Diaz JV, Slutsky AS, Villar J, Angus DC, et al. (October 2020). "Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis". JAMA. 324 (13): 1330–41. doi:10.1001/jama.2020.17023. PMC 7489434. PMID 32876694.

[177] "A parasitic infection that can turn fatal with administration of corticosteroids". WHO. 17 December 2021.

[pmid33844996-178] Ramakrishnan S, Nicolau DV, Langford B, Mahdi M, Jeffers H, Mwasuku C, Krassowska K, Fox R, Binnian I, Glover V, Bright S, Butler C, Cane JL, Halner A, Matthews PC, Donnelly LE, Simpson JL, Baker JR, Fadai NT, Peterson S, Bengtsson T, Barnes PJ, Russell RE, Bafadhel M (April 2021). "Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial". The Lancet. Respiratory Medicine. 9 (7): 763–772. doi:10.1016/S2213-2600(21)00160-0. PMC 8040526. PMID 33844996.

[pmid33844998-179] Agusti A, Torres F, Faner R (April 2021). "Early treatment with inhaled budesonide to prevent clinical deterioration in patients with COVID-19". The Lancet. Respiratory Medicine (Commentary). 9 (7): 682–683. doi:10.1016/S2213-2600(21)00171-5. PMC 8040539. PMID 33844998.

[180] "CAS-ViewAlert". www.cas.mhra.gov.uk. Retrieved 16 April 2021.

[pmid33471354-181] Deokar K, Agarwal M, Dutt N, Chauhan N, Niwas R, Shadrach BJ, Chawla G (2021). "A review of Ciclesonide in COVID-19. Still a long way to go". Advances in Respiratory Medicine. 89 (1): 79–81. doi:10.5603/ARM.a2020.0173. PMID 33471354.

[pmid33113146-182] Abobaker A, Alzwi A, Alraied AH (December 2020). "Overview of the possible role of vitamin C in management of COVID-19". Pharmacological Reports. 72 (6): 1517–28. doi:10.1007/s43440-020-00176-1. PMC 7592143. PMID 33113146.

[183] "Search of: vitamin C | Recruiting, Completed Studies | COVID-19". clinicaltrials.gov. Retrieved 14 November 2021.

[pmid34739908-184] Rawat D, Roy A, Maitra S, Gulati A, Khanna P, Baidya DK (October 2021). "Vitamin C and COVID-19 treatment: A systematic review and meta-analysis of randomized controlled trials". Diabetes & Metabolic Syndrome. 15 (6): 102324. doi:10.1016/j.dsx.2021.102324. PMC 8552785. PMID 34739908.

[185] "Vitamin C". National Institutes of Health. This article incorporates text from this source, which is in the public domain.

[pmid32758429-186] Martineau AR, Forouhi NG (September 2020). "Vitamin D for COVID-19: a case to answer?". The Lancet. Diabetes & Endocrinology. 8 (9): 735–6. doi:10.1016/S2213-8587(20)30268-0. PMC 7398646. PMID 32758429.

[187] "Vitamin D". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 17 July 2020. Retrieved 22 February 2021. This article incorporates text from this source, which is in the public domain.

[NICE2020-188] COVID-19 rapid guideline: vitamin D (PDF) (Technical report). National Institute for Health and Care Excellence (NICE). December 2020. ISBN 978-1-4731-3942-8. NG187. Retrieved 22 February 2021.

[189] Damascena AD, Azevedo LM, Oliveira TA, Santana JD, Pereira M (August 2021). "Addendum to vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis". Critical Reviews in Food Science and Nutrition: 1–6. doi:10.1080/10408398.2021.1951652. ISSN 1549-7852. PMID 34384300. S2CID 236997712.

[kazemi-190] Kazemi A, Mohammadi V, Aghababaee SK, Golzarand M, Clark CC, Babajafari S (March 2021). "Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis". Advances in Nutrition. 12 (5): 1636–1658. doi:10.1093/advances/nmab012. PMC 7989595. PMID 33751020.

[pmid33775818-191] Petrelli F, Luciani A, Perego G, Dognini G, Colombelli PL, Ghidini A (March 2021). "Therapeutic and prognostic role of vitamin D for COVID-19 infection: A systematic review and meta-analysis of 43 observational studies". The Journal of Steroid Biochemistry and Molecular Biology. 211: 105883. doi:10.1016/j.jsbmb.2021.105883. PMC 7997262. PMID 33775818.

[pmid33774074-192] Bassatne A, Basbous M, Chakhtoura M, Zein OE, Rahme M, Fuleihan GE (March 2021). "The link between COVID-19 and Vitamin D (VIVID): a systematic review and meta-analysis". Metabolism (Systematic review). 119: 154753. doi:10.1016/j.metabol.2021.154753. PMC 7989070. PMID 33774074.

[NICE_evidence-193] Evidence reviews for the use of vitamin D supplementation as prevention and treatment of COVID-19 (PDF) (Report). National Institute for Health and Care Excellence (NICE). December 2020.

[vitD-clintrials-194] "International clinical trials assessing vitamin D in people with COVID-19". ClinicalTrials.gov. Retrieved 11 June 2021.

[Quesada-Gomez-195] Quesada-Gomez JM, Entrenas-Castillo M, Bouillon R (September 2020). "Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166". The Journal of Steroid Biochemistry and Molecular Biology. 202: 105719. doi:10.1016/j.jsbmb.2020.105719. PMC 7289092. PMID 32535032.

[pmid33486522-196] Shah K, Saxena D, Mavalankar D (January 2021). "Vitamin D supplementation, COVID-19 & Disease Severity: A meta-analysis". QJM: Monthly Journal of the Association of Physicians. 114 (3): 175–181. doi:10.1093/qjmed/hcab009. PMC 7928587. PMID 33486522.

[pmid34029377-197] Stroehlein JK, Wallqvist J, Iannizzi C, Mikolajewska A, Metzendorf MI, Benstoem C, et al. (May 2021). "Vitamin D supplementation for the treatment of COVID-19: a living systematic review". The Cochrane Database of Systematic Reviews. 2021 (5): CD015043. doi:10.1002/14651858.CD015043. PMC 8406457. PMID 34029377. S2CID 235202971.{{cite journal}}: CS1 maint: PMC embargo expired (link)

[pmid31064117-198] Cesareo R, Falchetti A, Attanasio R, Tabacco G, Naciu AM, Palermo A (May 2019). "Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?". Nutrients (Review). 11 (5): 1016. doi:10.3390/nu11051016. PMC 6566727. PMID 31064117.

[199] "Zinc". Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health (NIH). 21 April 2021. Retrieved 28 November 2021. This article incorporates text from this source, which is in the public domain.

[200] Ansede M (3 April 2020). "Doscientos enfermos probarán un fármaco que ha bloqueado el coronavirus en minirriñones humanos". El País (in Spanish). Retrieved 3 April 2020.

[201] "Apeiron Biologics moves forward with APN01 for treatment of COVID-19". www.thepharmaletter.com. Retrieved 3 April 2020.

[202] "Coronavirus: Scientists could repurpose drugs to treat infection". Medical News Today. 28 February 2020. Retrieved 20 March 2020.

[203] "Existing Drugs May Offer a First-Line Treatment for Coronavirus Outbreak". Global Health News Wire. Retrieved 20 March 2020.

[Baron_105944-204] Baron SA, Devaux C, Colson P, Raoult D, Rolain JM (April 2020). "Teicoplanin: an alternative drug for the treatment of COVID-19?". International Journal of Antimicrobial Agents. 55 (4): 105944. doi:10.1016/j.ijantimicag.2020.105944. PMC 7102624. PMID 32179150.

[Andersen_2020-205] Andersen PI, Ianevski A, Lysvand H, Vitkauskiene A, Oksenych V, Bjørås M, et al. (April 2020). "Discovery and development of safe-in-man broad-spectrum antiviral agents". International Journal of Infectious Diseases. 93: 268–276. doi:10.1016/j.ijid.2020.02.018. PMC 7128205. PMID 32081774.

[Cuomo_2020-206] "Amid Ongoing COVID-19 Pandemic, Governor Cuomo Accepts Recommendation of Army Corps of Engineers for Four Temporary Hospital Sites in New York". governor.ny.gov. 22 March 2020.

[207] "Revive Therapeutics Announces U.S. FDA Approval of Confirmatory Phase 3 Clinical Trial for Bucillamine in COVID-19" (Press release). Revive Therapeutics Ltd. 31 July 2020. Retrieved 5 August 2020 – via GlobeNewswire.

[208] Favalli EG, Biggioggero M, Maioli G, Caporali R (September 2020). "Baricitinib for COVID-19: a suitable treatment?". The Lancet. Infectious Diseases. 20 (9): 1012–13. doi:10.1016/S1473-3099(20)30262-0. ISSN 1473-3099. PMC 7270794. PMID 32251638.

[FDA_Baricitinib-209] "Coronavirus (COVID-19) Update: FDA Authorizes Drug Combination for Treatment of COVID-19" (Press release). FDA. 19 November 2020. Retrieved 4 December 2020.

[Lilly_Baricitinib-210] "Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) of Baricitinib" (PDF). Indianapolis: Ely Lilly and Company. 19 November 2020. Retrieved 4 December 2020.

[211] "EMA starts evaluating use of Olumiant in hospitalised COVID-19 patients requiring supplemental oxygen" (Press release). European Medicines Agency (EMA). 29 April 2021. Retrieved 29 April 2021.

[FDA_Baricitinib_EUA-212] "Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021.

[FDA_Baricitinib_EUA_Fact_Sheet-213] "Fact Sheet for Baricitinib Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). July 2021.

[FDA_PR_20210730-214] "Coronavirus (COVID-19) Update: July 30, 2021". U.S. Food and Drug Administration (FDA) (Press release). 30 July 2021. Retrieved 30 July 2021. This article incorporates text from this source, which is in the public domain.

[215] Firth A, Prathapan P (1 January 2021). "Broad-spectrum therapeutics: A new antimicrobial class". Current Research in Pharmacology and Drug Discovery. 2: 100011. doi:10.1016/j.crphar.2020.100011. PMC 8035643. PMID 34870144.

[216] Firth A, Prathapan P (December 2020). "Azithromycin: The First Broad-spectrum Therapeutic". European Journal of Medicinal Chemistry. 207: 112739. doi:10.1016/j.ejmech.2020.112739. PMC 7434625. PMID 32871342.

[217] "Biodefense Strategic Plan | NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 2 February 2021.

[218] "NIH funds development of new broad-spectrum therapeutics". National Institutes of Health (NIH). 18 September 2015. Retrieved 2 February 2021.

[219] "New York clinical trial quietly tests heartburn remedy against coronavirus". Science. 26 April 2020.

[RadCan-220] "Début d'une étude clinique pour tester un médicament contre les effets de la COVID‑19 | Coronavirus". Radio-Canada.ca.

[COL-221] "COLCORONA Clinical Trial | Stop COVID-19". Colcorona.

[222] Ehrlich A, Uhl S, Ioannidis K, Hofree M, tenOever BR, Nahmias Y (14 July 2020). "The SARS-CoV-2 Transcriptional Metabolic Signature in Lung Epithelium". SSRN 3650499.

[223] "Antiviral Drug Reduces COVID-19 Inflammation In 48 Hours, Israeli Study Finds". 24 August 2021.

[224] "Cholesterol Drug May Downgrade COVID-19 Threat - New Study". 29 July 2020.

[225] "LIBERATE Trial in COVID-19 (LIBERATE)". ClinicalTrials.gov. Retrieved 10 September 2020.

[226] "Coronavirus: Ibuprofen tested as a treatment". BBC News Online. 3 June 2020. Retrieved 4 June 2020.

[227] Fink G, Orlova-Fink N, Schindler T, Grisi S, Ferrer AP, Daubenberger C, et al. (1 July 2020). "Inactivated trivalent influenza vaccine is associated with lower mortality among Covid-19 patients in Brazil (preprint)" (Document). doi:10.1101/2020.06.29.20142505. Covid-19 patients with recent influenza vaccination experience better health outcomes than non-vaccinated patients in Brazil. {{cite document}}: Cite document requires |publisher= (help); Unknown parameter |s2cid= ignored (help); Unknown parameter |work= ignored (help)

[228] "Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma". ClinicalTrials.gov. 5 March 2020. Retrieved 10 September 2020.

[229] Ning Q (14 March 2020). "A Pilot Study of Sildenafil in COVID-19". ClinicalTrials.gov. Retrieved 10 September 2020.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

[60]

[61]

[62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[70]

[71]

[72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82]

[83]

[84]

[85]

[86]

[87]

[88]

[89]

[90]

[91]

[92]

[93]

[94]

[95]

[96]

[97]

[98]

[99]

[100]

@@ Line 212: / Line 212: @@
 ==Further reading==
+* {{cite journal | vauthors=Banday AH, Shameem SA, Ajaz SJ| title=Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status. | journal=SLAS Discov | year= 2020 | volume= 25 | issue= 10 | pages= 1097–107 | pmid=32692266 | doi=10.1177/2472555220945281 | s2cid=220671335 | doi-access=free }}
-{{refbegin|30em}}
-* {{cite journal| vauthors=Banday AH, Shameem SA, Ajaz SJ| title=Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status. | journal=SLAS Discov | year= 2020 | volume= 25 | issue= 10 | pages= 1097–107 | pmid=32692266 | doi=10.1177/2472555220945281 | s2cid=220671335 | doi-access=free }}
+* {{cite journal | vauthors=Cantini F, Goletti D, Petrone L, Najafi Fard S, Niccoli L, Foti R |title=Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review |journal=Drugs |date=October 2020 |volume=80 |issue=18 |pages=1929–46 |pmid=33068263 |pmc=7568461 |doi=10.1007/s40265-020-01421-w |doi-access=free |title-link=doi }}
+* {{cite journal | vauthors=Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZ, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJ, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JC, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ |display-authors=6 |title=A SARS-CoV-2 protein interaction map reveals targets for drug repurposing |journal=Nature |volume=583 |issue=7816 |pages=459–68 |date=July 2020 |pmid=32353859 |doi=10.1038/s41586-020-2286-9 |pmc=7431030 |bibcode=2020Natur.583..459G |doi-access=free |title-link=doi }}
-* {{cite journal |vauthors=Cantini F, Goletti D, Petrone L, Najafi Fard S, Niccoli L, Foti R |title=Immune Therapy, or Antiviral Therapy, or Both for COVID-19: A Systematic Review |journal=Drugs |date=October 2020 |volume=80 |issue=18 |pages=1929–46 |pmid=33068263 |pmc=7568461 |doi=10.1007/s40265-020-01421-w |doi-access=free |title-link=doi }}
+* {{cite journal | vauthors=Guy RK, DiPaola RS, Romanelli F, Dutch RE |title=Rapid repurposing of drugs for COVID-19 |journal=Science |volume=368 |issue=6493 |pages=829–30 |date=May 2020 |pmid=32385101 |doi=10.1126/science.abb9332 |bibcode=2020Sci...368..829G |doi-access=free |title-link=doi }}
-* {{cite journal |vauthors=Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, O'Meara MJ, Rezelj VV, Guo JZ, Swaney DL, Tummino TA, Hüttenhain R, Kaake RM, Richards AL, Tutuncuoglu B, Foussard H, Batra J, Haas K, Modak M, Kim M, Haas P, Polacco BJ, Braberg H, Fabius JM, Eckhardt M, Soucheray M, Bennett MJ, Cakir M, McGregor MJ, Li Q, Meyer B, Roesch F, Vallet T, Mac Kain A, Miorin L, Moreno E, Naing ZZ, Zhou Y, Peng S, Shi Y, Zhang Z, Shen W, Kirby IT, Melnyk JE, Chorba JS, Lou K, Dai SA, Barrio-Hernandez I, Memon D, Hernandez-Armenta C, Lyu J, Mathy CJ, Perica T, Pilla KB, Ganesan SJ, Saltzberg DJ, Rakesh R, Liu X, Rosenthal SB, Calviello L, Venkataramanan S, Liboy-Lugo J, Lin Y, Huang XP, Liu Y, Wankowicz SA, Bohn M, Safari M, Ugur FS, Koh C, Savar NS, Tran QD, Shengjuler D, Fletcher SJ, O'Neal MC, Cai Y, Chang JC, Broadhurst DJ, Klippsten S, Sharp PP, Wenzell NA, Kuzuoglu-Ozturk D, Wang HY, Trenker R, Young JM, Cavero DA, Hiatt J, Roth TL, Rathore U, Subramanian A, Noack J, Hubert M, Stroud RM, Frankel AD, Rosenberg OS, Verba KA, Agard DA, Ott M, Emerman M, Jura N, von Zastrow M, Verdin E, Ashworth A, Schwartz O, d'Enfert C, Mukherjee S, Jacobson M, Malik HS, Fujimori DG, Ideker T, Craik CS, Floor SN, Fraser JS, Gross JD, Sali A, Roth BL, Ruggero D, Taunton J, Kortemme T, Beltrao P, Vignuzzi M, García-Sastre A, Shokat KM, Shoichet BK, Krogan NJ |display-authors=6 |title=A SARS-CoV-2 protein interaction map reveals targets for drug repurposing |journal=Nature |volume=583 |issue=7816 |pages=459–68 |date=July 2020 |pmid=32353859 |doi=10.1038/s41586-020-2286-9 |pmc=7431030 |bibcode=2020Natur.583..459G |doi-access=free |title-link=doi }}
-* {{cite journal |vauthors=Guy RK, DiPaola RS, Romanelli F, Dutch RE |title=Rapid repurposing of drugs for COVID-19 |journal=Science |volume=368 |issue=6493 |pages=829–30 |date=May 2020 |pmid=32385101 |doi=10.1126/science.abb9332 |bibcode=2020Sci...368..829G |doi-access=free |title-link=doi }}
+* {{cite journal | vauthors=Kotecha P, Light A, Checcucci E, Amparore D, Fiori C, Porpiglia F, Dasgupta P, Elhage O | display-authors=6 |title=Repurposing of drugs for Covid-19: a systematic review and meta-analysis |journal=Panminerva Med |date=October 2020 |pmid=33073552 |doi=10.23736/S0031-0808.20.04024-0 |doi-access=free | title-link=doi }}
+* {{cite journal | vauthors=Lamontagne F, Agoritsas T, Siemieniuk R, Rochwerg B, Bartoszko J, Askie L, Macdonald H, Amin W, Bausch FJ, Burhan E, Cecconi M, Chanda D, Dat VQ, Du B, Geduld H, Gee P, Nerina H, Hashimi M, Hunt BJ, Kabra S, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Leo YS, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Ranganathan SS, Sabzwari S, Sarin R, Sharland M, Shen Y, Souza JP, Stegemann M, Ugarte S, Venkatapuram S, Vuyiseka D, Preller J, Brignardello-Petersen R, Kum E, Qasim A, Zeraatkar D, Owen A, Guyatt G, Lytvyn L, Diaz J, Vandvik PO, Jacobs M | display-authors=6 |title=A living WHO guideline on drugs to prevent covid-19 |journal=The BMJ |date=2 March 2021 |volume=372 |pages=n526 |doi=10.1136/bmj.n526 |pmid=33649077 |s2cid=232081225|doi-access=free |title-link=doi }}
-* {{cite journal |vauthors=Kotecha P, Light A, Checcucci E, Amparore D, Fiori C, Porpiglia F, Dasgupta P, Elhage O | display-authors=6 |title=Repurposing of drugs for Covid-19: a systematic review and meta-analysis |journal=Panminerva Med |date=October 2020 |pmid=33073552 |doi=10.23736/S0031-0808.20.04024-0 |doi-access=free | title-link=doi }}
-* {{cite journal |vauthors=Lamontagne F, Agoritsas T, Siemieniuk R, Rochwerg B, Bartoszko J, Askie L, Macdonald H, Amin W, Bausch FJ, Burhan E, Cecconi M, Chanda D, Dat VQ, Du B, Geduld H, Gee P, Nerina H, Hashimi M, Hunt BJ, Kabra S, Kanda S, Kawano-Dourado L, Kim YJ, Kissoon N, Kwizera A, Leo YS, Mahaka I, Manai H, Mino G, Nsutebu E, Pshenichnaya N, Qadir N, Ranganathan SS, Sabzwari S, Sarin R, Sharland M, Shen Y, Souza JP, Stegemann M, Ugarte S, Venkatapuram S, Vuyiseka D, Preller J, Brignardello-Petersen R, Kum E, Qasim A, Zeraatkar D, Owen A, Guyatt G, Lytvyn L, Diaz J, Vandvik PO, Jacobs M | display-authors=6 |title=A living WHO guideline on drugs to prevent covid-19 |journal=The BMJ |date=2 March 2021 |volume=372 |pages=n526 |doi=10.1136/bmj.n526 |pmid=33649077 |s2cid=232081225|doi-access=free |title-link=doi }}
 * {{cite journal | vauthors=McCreary EK, Pogue JM | title=Coronavirus Disease 2019 Treatment: A Review of Early and Emerging Options | journal=Open Forum Infectious Diseases | volume=7 | issue=4 | pages=ofaa105 | date=April 2020 | pmid=32284951 | pmc=7144823 | doi=10.1093/ofid/ofaa105 | doi-access=free |title-link=doi }}
-* {{cite journal |vauthors=Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, Pardo-Hernandez H, Rochwerg B, Lamontagne F, Han MA, Liu Q, Agarwal A, Agoritsas T, Chu DK, Couban R, Darzi A, Devji T, Fang B, Fang C, Flottorp SA, Foroutan F, Heels-Ansdell D, Honarmand K, Hou L, Hou X, Ibrahim Q, Loeb M, Marcucci M, McLeod SL, Motaghi S, Murthy S, Mustafa RA, Neary JD, Qasim A, Rada G, Riaz IB, Sadeghirad B, Sekercioglu N, Sheng L, Sreekanta A, Switzer C, Tendal B, Thabane L, Tomlinson G, Turner T, Vandvik PO, Vernooij RW, Viteri-García A, Wang Y, Yao L, Ye Z, Guyatt GH, Brignardello-Petersen R |display-authors=6 |title=Drug treatments for covid-19: living systematic review and network meta-analysis |journal=BMJ |volume=370 |pages=m2980 |date=July 2020 |pmid=32732190 |pmc=7390912 |doi=10.1136/bmj.m2980 |doi-access=free |title-link=doi }}
+* {{cite journal | vauthors=Siemieniuk RA, Bartoszko JJ, Ge L, Zeraatkar D, Izcovich A, Kum E, Pardo-Hernandez H, Rochwerg B, Lamontagne F, Han MA, Liu Q, Agarwal A, Agoritsas T, Chu DK, Couban R, Darzi A, Devji T, Fang B, Fang C, Flottorp SA, Foroutan F, Heels-Ansdell D, Honarmand K, Hou L, Hou X, Ibrahim Q, Loeb M, Marcucci M, McLeod SL, Motaghi S, Murthy S, Mustafa RA, Neary JD, Qasim A, Rada G, Riaz IB, Sadeghirad B, Sekercioglu N, Sheng L, Sreekanta A, Switzer C, Tendal B, Thabane L, Tomlinson G, Turner T, Vandvik PO, Vernooij RW, Viteri-García A, Wang Y, Yao L, Ye Z, Guyatt GH, Brignardello-Petersen R |display-authors=6 |title=Drug treatments for covid-19: living systematic review and network meta-analysis |journal=BMJ |volume=370 |pages=m2980 |date=July 2020 |pmid=32732190 |pmc=7390912 |doi=10.1136/bmj.m2980 |doi-access=free |title-link=doi }}
+* {{cite journal |vauthors=Tummino TA, Rezelj VV, Fischer B, Fischer A, O'Meara MJ, Monel B, Vallet T, White KM, Zhang Z, Alon A, Schadt H, O'Donnell HR, Lyu J, Rosales R, McGovern BL, Rathnasinghe R, Jangra S, Schotsaert M, Galarneau JR, Krogan NJ, Urban L, Shokat KM, Kruse AC, García-Sastre A, Schwartz O, Moretti F, Vignuzzi M, Pognan F, Shoichet BK | display-authors=6 |title=Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2 |journal=Science |volume=373 |issue=6554 |pages=541–7 |date=July 2021 |pmid=34326236 |doi=10.1126/science.abi4708 }}
-* {{cite news | vauthors=Velasquez-Manoff M | title=How Covid Sends Some Bodies to War With Themselves | website=[[The New York Times]] | date=11 August 2020 | url=https://www.nytimes.com/2020/08/11/magazine/covid-cytokine-storms.html }}
-* {{cite news | vauthors=Zimmer C | title=Old Drugs May Find a New Purpose: Fighting the Coronavirus | website=[[The New York Times]] | date=30 April 2020 | url=https://www.nytimes.com/2020/04/30/health/coronavirus-antiviral-drugs.html |ref=none }}
-{{refend}}
 ==External links==
@@ Line 231: / Line 228: @@
 * {{cite web | title=JHMI Clinical Recommendations for Available Pharmacologic Therapies for COVID-19 | website=Johns Hopkins Medicine | url=https://www.hopkinsguides.com/hopkins/ub?cmd=repview&type=479-1225&name=30_538747_PDF | format=PDF }}
 * {{cite report | vauthors=((World Health Organization)) | title=Therapeutics and COVID-19: living guideline, 24 September 2021 | publisher=[[World Health Organization]] (WHO) | author-link=World Health Organization | year=2021 | id=WHO/2019-nCoV/therapeutics/2021.3 | hdl=10665/345356 | hdl-access=free }}
+* {{cite news | vauthors=Velasquez-Manoff M | title=How Covid Sends Some Bodies to War With Themselves | website=[[The New York Times]] | date=11 August 2020 | url=https://www.nytimes.com/2020/08/11/magazine/covid-cytokine-storms.html }}
+* {{cite news | vauthors=Zimmer C | title=Old Drugs May Find a New Purpose: Fighting the Coronavirus | website=[[The New York Times]] | date=30 April 2020 | url=https://www.nytimes.com/2020/04/30/health/coronavirus-antiviral-drugs.html }}
 {{COVID-19 pandemic}}