SARS-CoV-2
The novel coronavirus (2019-nCoV), also known as the Wuhan coronavirus[1] and named Covid-19 by WHO, 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. Genomic sequencing has shown that it is a positive-sense, single-stranded RNA coronavirus.
Due to reports that 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. Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to SARS-CoV (79.5%) and bat coronaviruses (96%),[2] with a likely origin in bats being theorized.[3][4]
Epidemiology
The first known human infection occurred in early December 2019. Molecular clock approaches suggest a similar, or slightly earlier, date of origin.
An outbreak of 2019-nCoV was first 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.
As of 29 January 2020 (04:00 UTC), there were 6,057 confirmed cases of infection, of which 5,970 were within mainland China. 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. The number of deaths was 132 as of 29 January 2020 (04:00 UTC).[5] Human-to-human spread was first confirmed in Guangdong, China, on 20 January 2020.
Treatment
No specific treatment is currently available, so treatment is focused on alleviation of symptoms,[6] which include fever, fatigue, dry cough, and shortness of breath, or pneumonia and kidney failure in severe cases. The Chinese Center for Disease Control and Prevention (CCDC) is testing existing pneumonia treatments for efficacy in treating coronavirus-related pneumonia.
Existing anti-virals are being studied, including protease inhibitors like indinavir, saquinavir, remdesivir, lopinavir/ritonavir and interferon beta. The effectiveness of previously identified monoclonal antibodies (mAbs) is also under investigation.
Virology
Infection
Human-to-human transmission of the virus has been confirmed.[7] Reports have emerged that the virus is infectious even during the incubation period, although as of 27 January 2020 officials at the Centers for Disease Control and Prevention (CDC) in the United States stated they "don't have any evidence of patients being infectious prior to symptom onset."
Research groups have estimated the basic reproduction number (<math>R_0</math>, pronounced R-nought) of the virus to be between 1.4 and 5, with most estimates below 3.8. This means that, when unchecked, the virus typically results in 1.4 to 3.8 new cases per established infection. It has been established that the virus is able to transmit along a chain of at least four people.
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.[8] A market selling live animals for food was also blamed in the SARS epidemic in 2003; such markets are considered to be incubators for novel pathogens. The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.
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. 2019-nCoV 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. A third unpublished virus genome from Rhinolophus affinis, "RaTG13", is said to have a 96% resemblance to 2019-nCoV. 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.
Phylogenetics and taxonomy
| File:2019-nCoV genome.svg Genome organisation (click to enlarge) | |
| NCBI genome ID | MN908947 |
|---|---|
| Genome size | 29,903 bases |
| Year of completion | 2020 |
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.
Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus Sarbecovirus (Beta-CoV lineage B).[8] Its RNA sequence is approximately 30 kb in length.[9]
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;[9] 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.
Structural biology
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. 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.
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, and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.
Vaccine research
In January 2020, several organizations and institutions began work on creating vaccines for 2019 n-CoV based on the published genome.[11][12]
In China, the Chinese Center for Disease Control and Prevention is developing a vaccine against the novel coronavirus.[13] The team of Yuen Kwok-yung at the University of Hong Kong, which previously participated in work on the SARS coronavirus during its 2003 outbreak, has also announced that a vaccine is under development there but has yet to proceed to animal testing.
Elsewhere, 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.[14] 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.[11] 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.[14]
In an independent project, the Public Health Agency of Canada has granted permission to the International Vaccine Centre (VIDO-InterVac) at the University of Saskatchewan to begin work on a vaccine. VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.[12]
References
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