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SARS-CoV-2

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Novel coronavirus (2019-nCoV)
Transmission electron micrograph of two 2019-nCoV virions
Transmission electron micrograph of two 2019-nCoV virions
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Virus:
Novel coronavirus (2019-nCoV)
SARS-CoV-2 is located in China
SARS-CoV-2
Wuhan, China, the epicentre of the only recorded outbreak
Synonyms

The 2019 novel coronavirus (2019-nCoV)[3][4], also known as the Wuhan coronavirus,[1] is a contagious virus that causes respiratory infection and has shown evidence of human-to-human transmission, first identified by authorities in Wuhan, Hubei, China, as the cause of the ongoing 2019-20 Wuhan coronavirus outbreak.[5] Genomic sequencing has shown that it is a positive-sense, single-stranded RNA coronavirus.[6][7][8]

Due to reports that the the initial cases had epidemiological links to a large seafood and animal market, the virus is thought to have a zoonotic origin, though this has not been confirmed.[9] Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to SARS-CoV (79.5%)[10] and bat coronaviruses (96%)[10], with a likely origin in bats being theorized.[11][12][13]

Epidemiology

The first known outbreak of 2019-nCoV was detected in Wuhan, China, in mid-December 2019. The virus subsequently spread to other provinces of Mainland China and other countries, including Thailand, Japan, Taiwan, South Korea, Australia, France, and the United States.[14][15][16]

As of 27 January 2020, there were 2,886 confirmed cases of infection, of which 2,825 were within mainland China.[17] Cases outside China, to date, were people who have either travelled from Wuhan, or were in direct contact with someone who travelled from the area.[18] The number of deaths was 81 as of 27 January 2020.[17] Human-to-human spread was confirmed in Guangdong, China, on 20 January 2020.[19]

Symptoms

Symptoms of 2019-nCoV (Wuhan coronavirus).

Reported symptoms have included fever, fatigue, dry cough, shortness of breath, and respiratory distress.[20][21] Cases of severe infection can result in pneumonia, kidney failure, and death.[22] In a statement issued on 23 January 2020, WHO Director-General Tedros Adhanom Ghebreyesus stated that a quarter of those infected experienced severe disease, and that many of those who died had other conditions such as hypertension, diabetes, or cardiovascular disease that impaired their immune systems.[23] A study of the first 41 patients admitted to hospitals in Wuhan with confirmed cases reported that a majority of the patients were healthy before contracting the infection, and that over a quarter of previously healthy individuals required intensive care.[24][25] Among the majority of those hospitalised, vital signs were stable on admission, and they had low white blood cells counts and low lymphocytes.[21]

Treatment

No specific treatment is currently available, so treatment is focused on alleviation of symptoms.[26] The Chinese Center for Disease Control and Prevention (CCDC) is testing existing drug effectiveness for pneumonia.[27]

Existing anti-virals are being studied,[26] including protease inhibitors like indinavir, saquinavir, remdesivir, lopinavir/ritonavir and interferon beta.[28][29] The effectiveness of previously identified monoclonal antibodies (mAbs) is also under investigation.[30]

Virology

Infection

Human-to-human transmission of the virus has been confirmed.[19] Reports have emerged that the virus is infectious even during the incubation period.[31][32] However, officials at the Centers for Disease Control and Prevention (CDC) in the United States have stated that they "don't have any evidence of patients being infectious prior to symptom onset."[33]

One research group has estimated the basic reproduction number () of the virus to be between 3 and 5,[34] meaning it typically infects 3 to 5 people per established infection. Other research groups have estimated the basic reproduction number to be between 1.4 and 3.8.[35] It has been established that the virus is able to transmit along a chain of at least four people.[36]

Reservoir

Animals sold for food are suspected to be the reservoir or the intermediary because many of the first identified infected individuals were workers at the Huanan Seafood Market. Consequently, they were exposed to greater contact with animals.[21] A market selling live animals for food was also blamed in the SARS epidemic in 2003; such markets are considered a perfect incubator for novel pathogens.[37]

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. During 17 years of research on the origin of the SARS 2003 epidemic, many SARS-like bat coronaviruses were isolated and sequenced, most of them originating from the Rhinolophus genus of bats. The Wuhan novel coronavirus has been found to fall into this category of SARS-related coronaviruses. Two genome sequences from Rhinolophus sinicus published in 2015 and 2017 show a resemblance of 80% to 2019-nCoV.[11][12] A third unpublished virus genome from Rhinolophus affinis "RaTG13" with a resemblance of 96% to 2019-nCoV has also been noted.[38] For comparison, this amount of variation among viruses is similar to the amount of mutation observed over ten years in the H3N2 human flu virus strain.[39]

Phylogenetics and taxonomy

Genomic information
Genome organisation (click to enlarge)
NCBI genome IDMN908947
Genome size30,473 bases
Year of completion2020

2019-nCoV belongs to the broad family of viruses known as coronaviruses. Other coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as the Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and SARS-CoV.[40]

Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-COV, a member of the subgenus Sarbecovirus (Beta-CoV lineage B).[41][21][42] Its RNA sequence is approximately 30 kb in length.[8]

By 12 January, five genomes of the novel coronavirus had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention and other institutions;[8][43][44] the number of genomes increased to 28 by 26 January. Except for the earliest GenBank genome, the genomes are under an embargo at GISAID. A phylogenic analysis for the samples is available through Nextstrain.[45]

Structural biology

Innophore Phyre2 ribbon diagram of 2019-nCoV protease, a prospective target for antiviral drugs[46]

The publications of the genome led to several protein modeling experiments on the receptor binding protein (RBD) of the nCoV spike (S) protein suggesting that the S protein retained sufficient affinity to the Angiotensin converting enzyme 2 (ACE2) receptor to use it as a mechanism of cell entry.[47] On 22 January, a group in China working with the full virus and a group in the U.S. working with reverse genetics independently and experimentally demonstrated ACE2 as the receptor for 2019-nCoV.[48][49][50]

To look for potential protease inhibitors, the viral 3C-like protease M(pro) from the Orf1a polyprotein was also modeled for drug docking experiments. Innophore has produced two computational models based on SARS protease,[46] and the Chinese Academy of Sciences (Rao ZH, Yang HT) has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.[51]

Vaccine research

In January 2020, several organizations and institutions began work on creating vaccines for the Wuhan coronavirus based on the published genome.[52][53] In China, the CCDC has started developing vaccines against the novel coronavirus.[54][55]

Three vaccine projects are being supported by the Coalition for Epidemic Preparedness Innovations (CEPI), including one project by the biotechnology company Moderna and another by the University of Queensland.[56] The United States National Institutes of Health (NIH) is cooperating with Moderna to create an RNA vaccine matching a spike of the coronavirus surface, and is hoping to start production by May 2020.[52] In Australia, the University of Queensland is investigating the potential of a molecular clamp vaccine that would genetically modify viral proteins to make them mimic the coronavirus and stimulate an immune reaction.[56]

In an independent project, the Public Health Agency of Canada has granted permission to the Vaccine and Infectious Disease Organization – International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan to begin work on a vaccine.[57] VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.[53]

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External links