COVID-19 drug repurposing research

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Drug repositioning (also called drug repurposing) – the investigation of existing drugs for new therapeutic purposes – is one line of scientific research which is followed to develop safe and effective COVID-19 treatments.[1][2] Other research directions include the development of a COVID-19 vaccine.

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, are being researched as COVID-19 treatments, with some moving into clinical trials.[3]

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".[1]

Drug repurposing[edit]

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 another disease or medical condition.[4]

Reusing approved medications has the following benefits:

  • Faster legislative and medical approval[citation needed]
  • Existing body of scientific literature (particularly Contraindications and Drug Interactions)[citation needed]

Studies[edit]

Chloroquine[edit]

Chloroquine is an anti-malarial medication that is also used against some auto-immune diseases. On 18 March, the WHO announced that chloroquine and the related hydroxychloroquine would be among the four drugs studied as part of the Solidarity clinical trial.[5] New York governor Andrew Cuomo announced that New York State trials of chloroquine and hydroxychloroquine would begin on 24 March.[6]

Favipiravir[edit]

Chinese clinical trials in Wuhan and Shenzhen claimed to show that favipiravir, was "clearly effective". One Japanese public health official said the drug may be less effective in severe cases.[7]

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.[8] The Italian Pharmaceutical Agency reminded the public that the existing evidence in support of the drug is scant and preliminary.[9]

Interferon beta[edit]

A UK firm started conducting trials on IFN-β, a drug that was originally developed to treat COPD.[5]

Lopinavir/ritonavir[edit]

One study of lopinavir/ritonavir (Keletra), a combination of the antivirals lopinavir and ritonavir, concluded that "no benefit was observed".[10][11] 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 COVID-19.[12]

There are criticisms within the scientific community about directing resources to repurposing drugs specifically developed for HIV/AIDS, since it is unlikely that a drug developed specifically against HIV will work for a very different virus (it is more likely that general-purpose antivirals will work).[1] The WHO included lopinavir/ritonavir in the international Solidarity trial.[5]

Remdesivir[edit]

Cleveland University Hospitals started conducting two clinical trials for remdesivir, one for people with moderate illness and another for those with more severe illness.[13] The Feinstein Institute of the Northwell Health system partnered with Gilead Sciences on phase III clinical trials for remdesivir.[14]

Intravenous vitamin C[edit]

There are three ongoing clinical trials of intravenous vitamin C for people who are hospitalized and severely ill with COVID-19; two placebo controlled (China, Canada) and one with no control (Italy).[15] A review of vitamin C administration to critically ill patients (burns, trauma, sepsis) reported a tendency towards a mortality reduction when intravenous, high-dose, vitamin C monotherapy was administered.[16] Intravenous vitamin C achieves a much higher plasma and tissue content than is possible with orally consumed vitamin C.[17]

Azithromycin[edit]

New York State began trials for azithromycin on 24 March.[18]

Ciclesonide[edit]

Japan's National Center for Global Health and Medicine (NCGM) is planning a clinical trial for Teijin's Alvesco (ciclesonide), an inhaled corticosteroid for asthma, for the treatment of pre-symptomatic patients infected with the novel coronavirus. [19]

Repurposed drugs[edit]

Antiviral drugs[edit]

Since SARS-CoV-2 is a virus, considerable scientific attention has been focused on repurposing approved anti-viral drugs that were developed for prior outbreaks such as MERS, SARS, and West Nile virus.[citation needed]

Anti malarial agents[edit]

Broad-spectrum agents[edit]

  • Ribavirin: ribavirin was recommended for COVID-19 treatment according to Chinese 7th edition guidelines[22]
  • Umifenovir: umifenovir was recommended for COVID-19 treatment according to Chinese 7th edition guidelines[22]

Interferons[edit]

Drugs originally developed for SARS[edit]

  • APN01 (ACE2 protein decoy)[26]

Antibiotics[edit]

Some antibiotics that have been identified as potentially repurposable as COVID-19 treatments:[27][28]

Research progression[edit]

Table key
Symbol Meaning
✔️ Significant anti-viral activity
No Significant anti-viral activity
? Ongoing study


Drug name Original use Status (as COVID-19 treatment)
Trials Studies Randomized clinical trial (RCT) Approved

for COVID-19

Cell cultures
or co-cultures

(In-vitro)

Human
primary cells
or organoids

(Ex vivo)

Animal models Open label Phase 0 Phase I Phase II Phase III Phase IV
Hydroxychloroquine Anti-malarial ✔️[31] ?[32][30] ✔️ FDA EUA[33]
Chloroquine Anti-malarial ✔️[20] ✔️ FDA EUA[33]
Favipiravir Broad-spectrum anti-viral [20] ✔️[34] ✔️[35] ✔️ in Japan[30]
Lopinavir/ritonavir HIV protease inhibitor combination [36][37]
Remdesivir Novel broad-spectrum anti-viral ✔️[20] ?[38]
Ribavirin Broad-spectrum anti-viral [20]
Umifenovir Broad-spectrum anti-viral ?[39][30]
Lopinavir HIV protease inhibitor [36] ?[39][30]
Ritonavir HIV protease inhibitor [36] ?[39][30]
Cepharanthine Anti-inflammatory compound[40] ✔️[41][30]
Mefloquine Anti-malarial ✔️[41][30]
Penciclovir Herpesvirus anti-viral [20]
Nitazoxanide Broad-spectrum anti-viral, antiparasitic ✔️[20]
Nafamostat Synthetic serine protease inhibitor [20]
Selamectin Antiparasitic and anthelmintic ✔️[41][30]
Corticosteroids Steroid hormone ?[42]
Emtricitabine/tenofovir HIV reverse transcriptase inhibitor ?[43]
Teicoplanin Antibiotic ✔️[29]
Ciclesonide Lipid-Conjugated Corticosteroid ✔️[44] ?[45]

See also[edit]

References[edit]

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Further reading[edit]

  • McCreary, Erin K; Pogue, Jason M (23 March 2020). "COVID-19 Treatment: A Review of Early and Emerging Options". Open Forum Infectious Diseases. doi:10.1093/ofid/ofaa105. ISSN 2328-8957.

External links[edit]