SARS-CoV-2

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The novel coronavirus (2019-nCoV),[1][2] also known as the Wuhan coronavirus,[3] 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.[4] Genomic sequencing has shown that it is a positive-sense, single-stranded RNA coronavirus.[5][6][7]

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.[8] Comparisons of genetic sequences between this virus and other existing virus samples have shown similarities to SARS-CoV (79.5%)[9] and bat coronaviruses (96%),[9] with a likely origin in bats being theorized.[10][11][12]

Epidemiology

Main article: 2019–20 Wuhan coronavirus outbreak

The first known human infection occurred in early December 2019. Molecular clock approaches suggest a similar, or slightly earlier, date of origin.[13]

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.[14][15][16]

As of 29 January 2020 (04:00 UTC), there were 6,057 confirmed cases of infection, of which 5,970 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 132 as of 29 January 2020 (04:00 UTC).[17] Human-to-human spread was first confirmed in Guangdong, China, on 20 January 2020.[19]

Treatment

No specific treatment is currently available, so treatment is focused on alleviation of symptoms,[20] which include fever, fatigue, dry cough, and shortness of breath, or pneumonia and kidney failure in severe cases.[21][22][23] The Chinese Center for Disease Control and Prevention (CCDC) is testing existing pneumonia treatments for efficacy in treating coronavirus-related pneumonia.[24]

Existing anti-virals are being studied,[20] including protease inhibitors like indinavir, saquinavir, remdesivir, lopinavir/ritonavir and interferon beta.[25][26][27] The effectiveness of previously identified monoclonal antibodies (mAbs) is also under investigation.[28]

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,[29][30] 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."[31][32]

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.[33][34][35][36] 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.[37]

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.[22] 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.[38] The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.[39]

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.[10][11] A third unpublished virus genome from Rhinolophus affinis, "RaTG13", is said to have a 96% resemblance to 2019-nCoV.[40] 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.[41]

Phylogenetics and taxonomy

Genomic information
File:2019-nCoV genome.svg
Genome organisation (click to enlarge)
NCBI genome IDMN908947
Genome size29,903 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.[42]

Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus Sarbecovirus (Beta-CoV lineage B).[43][22][44] Its RNA sequence is approximately 30 kb in length.[7]

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;[7][45][46] 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.[47]

Structural biology

File:Coronavirus 2019-nCoV.3.png
Innophore Phyre2 ribbon diagram of the 2019-nCoV M(pro) protease, a prospective target for antiviral drugs[48]

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.[49] 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.[50][51][52]

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,[48] and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.[53]

Vaccine research

In January 2020, several organizations and institutions began work on creating vaccines for 2019 n-CoV based on the published genome.[54][55]

In China, the Chinese Center for Disease Control and Prevention is developing a vaccine against the novel coronavirus.[24][56] 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.[57]

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.[58] 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.[54] 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.[58]

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.[59] VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.[55]

References

  1. ↑ "Surveillance case definitions for human infection with novel coronavirus (nCoV)". World Health Organization. Retrieved 21 January 2020.
  2. ↑ "Novel coronavirus (2019-nCoV), Wuhan, China". United States: Centers for Disease Control and Prevention. 10 January 2020. Retrieved 16 January 2020. Unknown parameter |url-status= ignored (help)
  3. ↑
  4. ↑ "2019 Novel Coronavirus (2019 nCoV): Frequently Asked Questions | IDPH". www.dph.illinois.gov. Retrieved 2020-01-27.
  5. ↑ "中国疾病预防控制中心" (in Chinese). People's Republic of China: Chinese Center for Disease Control and Prevention. Retrieved 9 January 2020.
  6. ↑ "New-type coronavirus causes pneumonia in Wuhan: expert". People's Republic of China. Xinhua. Retrieved 9 January 2020.
  7. ↑ 7.0 7.1 7.2 "CoV2020". platform.gisaid.org. Retrieved 12 January 2020. Unknown parameter |url-status= ignored (help)
  8. ↑ http://www.nj.gov/health/cd/documents/topics/NCOV/NCoV_LINCS_wuhan_update_011820_combined.pdf
  9. ↑ 9.0 9.1 Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui (23 January 2020). "Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin". bioRxiv: 2020.01.22.914952. doi:10.1101/2020.01.22.914952 – via www.biorxiv.org.
  10. ↑ 10.0 10.1 Sample CoVZC45 and CoVZXC21, see there for an interactive visualisation
  11. ↑ 11.0 11.1 "The 2019 new Coronavirus epidemic: evidence for virus evolution". doi:10.1101/2020.01.24.915157v1 (inactive 2020-01-25).
  12. ↑ Callaway, Ewen; Cyranoski, David (2020-01-23). "Why snakes probably aren't spreading the new China virus". Nature. doi:10.1038/d41586-020-00180-8.
  13. ↑ Cohen, Jon (26 January 2020). "Wuhan seafood market may not be source of novel virus spreading globally". Science | AAAS.
  14. ↑ "China coronavirus: Hong Kong widens criteria for suspected cases after second patient confirmed, as MTR cancels Wuhan train ticket sales". Hong Kong: South China Morning Post. 23 January 2020. Retrieved 23 January 2020.
  15. ↑ "Novel coronavirus: three cases reported in France". European Centre for Disease Prevention and Control. 25 January 2020.
  16. ↑ Doherty, Ben (25 January 2020). "Coronavirus: three cases in NSW and one in Victoria as infection reaches Australia". The Guardian. ISSN 0261-3077. Retrieved 26 January 2020.
  17. ↑ 17.0 17.1 "Operations Dashboard for ArcGIS". gisanddata.maps.arcgis.com. Retrieved 28 January 2020.
  18. ↑ "Novel Coronavirus (2019-nCoV) SITUATION REPORT - 5 25 JANUARY 2020" (PDF). Retrieved 26 January 2020.
  19. ↑ 19.0 19.1 "China confirms human-to-human transmission of new coronavirus". Canadian Broadcasting Corporation. 20 January 2020. Retrieved 21 January 2020. Unknown parameter |url-status= ignored (help)
  20. ↑ 20.0 20.1 "WHO says new China coronavirus could spread, warns hospitals worldwide". Reuters. 14 January 2020. Retrieved 21 January 2020.
  21. ↑ "Experts explain the latest bulletin of unknown cause of viral pneumonia". Wuhan Municipal Health Commission. 11 January 2020. Archived from the original on 11 January 2020. Retrieved 11 January 2020. Unknown parameter |url-status= ignored (help)
  22. ↑ 22.0 22.1 22.2 Hui DS, I Azhar E, Madani TA, Ntoumi F, Kock R, Dar O, Ippolito G, Mchugh TD, Memish ZA, Drosten C, Zumla A, Petersen E. The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health – The latest 2019 novel coronavirus outbreak in Wuhan, China. Int J Infect Dis. 2020 Jan 14;91:264–266. doi:10.1016/j.ijid.2020.01.009. PMID 31953166.open access publication – free to read
  23. ↑ "Q&A on coronaviruses". www.who.int. Retrieved 2020-01-27.
  24. ↑ 24.0 24.1 "China CDC developing novel coronavirus vaccine". Xinhua. 2020-01-26.
  25. ↑ Xu, Zhijian; Peng, Cheng; Shi, Yulong; Zhu, Zhengdan; Mu, Kaijie; Wang, Xiaoyu; Zhu, Weiliang (28 January 2020). "Nelfinavir was predicted to be a potential inhibitor of 2019 nCov main protease by an integrative approach combining homology modelling, molecular docking and binding free energy calculation". bioRxiv: 2020.01.27.921627. doi:10.1101/2020.01.27.921627 – via www.biorxiv.org.
  26. ↑ Paules, Catharine I.; Marston, Hilary D.; Fauci, Anthony S. (23 January 2020). "Coronavirus Infections—More Than Just the Common Cold". JAMA. doi:10.1001/jama.2020.0757. PMID 31971553.
  27. ↑ "Gilead assessing Ebola drug as possible coronavirus treatment". Reuters. 2020-01-23. Retrieved 2020-01-26.
  28. ↑ "Coronavirus: Vir Biotechnology and Novavax announce vaccine plans-GB". Retrieved 2020-01-26.
  29. ↑ "【武漢肺炎】衛健委︰新型冠狀病毒傳播力增強　潛伏期最短僅1天". 明報新聞網 (in CN).
  30. ↑ "专家：病毒潜伏期有传染性 有人传染同事后才发病". news.163.com (in CN). 26 January 2020.
  31. ↑ "U.S. Notches Fifth Coronavirus Case as Global Count Nears 3,000". www.medpagetoday.com. 27 January 2020.
  32. ↑ "Transcript of 2019 Novel Coronavirus (2019-nCoV) Update | CDC Online Newsroom | CDC". www.cdc.gov. 28 January 2020.
  33. ↑ "The Deceptively Simple Number Sparking Coronavirus Fears". The Atlantic. 28 January 2020.
  34. ↑ Liu, Tao; Hu, Jianxiong; Kang, Min; Lin, Lifeng; Zhong, Haojie; Xiao, Jianpeng; He, Guanhao; Song, Tie; Huang, Qiong; Rong, Zuhua; Deng, Aiping; Zeng, Weilin; Tan, Xiaohua; Zeng, Siqing; Zhu, Zhihua; Li, Jiansen; Wan, Donghua; Lu, Jing; Deng, Huihong; He, Jianfeng; Ma, Wenjun (2020-01-25). "Transmission dynamics of 2019 novel coronavirus (2019-nCoV)". bioRxiv: 2020.01.25.919787. doi:10.1101/2020.01.25.919787.
  35. ↑ Zhao, Shi; Ran, Jinjun; Musa, Salihu Sabiu; Yang, Guangpu; Lou, Yijun; Gao, Daozhou; Yang, Lin; He, Daihai (2020-01-24). "Preliminary estimation of the basic reproduction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven analysis in the early phase of the outbreak". bioRxiv: 2020.01.23.916395. doi:10.1101/2020.01.23.916395.
  36. ↑ Read, Jonathan M.; Bridgen, Jessica RE; Cummings, Derek AT; Ho, Antonia; Jewell, Chris P. (2020-01-28). "Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic predictions". medRxiv: 2020.01.23.20018549. doi:10.1101/2020.01.23.20018549.
  37. ↑ Saey, Tina Hesman (24 January 2020). "How the new coronavirus stacks up against SARS and MERS". Archived from the original on 25 January 2020. Retrieved 25 January 2020. Unknown parameter |url-status= ignored (help)
  38. ↑ Myers, Steven Lee (January 25, 2020). "China's Omnivorous Markets Are in the Eye of a Lethal Outbreak Once Again". The New York Times. Unknown parameter |url-status= ignored (help)
  39. ↑ Template:Cite
  40. ↑ Wuhan Institue of Virology (23 January 2020). "Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin". bioRxiv. doi:10.1101/2020.01.22.914952v2 (inactive 2020-01-25). Retrieved 24 January 2020. (BetaCoV/bat/Yunnan/RaTG13/2013; available on GISAID)
  41. ↑ "Real-time tracking of influenza A/H3N2 evolution using data from GISAID". nextstrain.org.
  42. ↑ Zhu, Na; Zhang, Dingyu; Wang, Wenling; Li, Xinwang; Yang, Bo; Song, Jingdong; Zhao, Xiang; Huang, Baoying; Shi, Weifeng; Lu, Roujian; Niu, Peihua; Zhan, Faxian; Ma, Xuejun; Wang, Dayan; Xu, Wenbo; Wu, Guizhen; Gao, George F.; Tan, Wenjie (24 January 2020). "A Novel Coronavirus from Patients with Pneumonia in China, 2019". New England Journal of Medicine. United States. 0. doi:10.1056/NEJMoa2001017. ISSN 0028-4793.
  43. ↑ "Phylogeny of SARS-like betacoronaviruses". nextstrain. Retrieved 18 January 2020.
  44. ↑ Antonio C. P. Wong, Xin Li, Susanna K. P. Lau, Patrick C. Y. Woo. Global Epidemiology of Bat Coronaviruses. Viruses. 2019 Feb;11(2):174. doi:10.3390/v11020174.
  45. ↑ "Initial genome release of novel coronavirus". Virological. 11 January 2020. Retrieved 12 January 2020.
  46. ↑ "Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome". National Center for Biotechnology Information. United States: National Institutes of Health. 17 January 2020.
  47. ↑ Bedford, Trevor; Neher, Richard. "Genomic epidemiology of novel coronavirus (nCoV) using data generated by Fudan University, China CDC, Chinese Academy of Medical Sciences, Chinese Academy of Sciences, Zhejiang Provincial Center for Disease Control and Prevention and the Thai National Institute of Health shared via GISAID". nextstrain.org. Retrieved 26 January 2020. Unknown parameter |url-status= ignored (help)
  48. ↑ 48.0 48.1 Gruber, Christian; Steinkellner, Georg (23 January 2020). "Wuhan coronavirus 2019-nCoV - what we can find out on a structural bioinformatics level". Innophore Enzyme Discovery. Innophore GmbH. doi:10.6084/m9.figshare.11752749.
  49. ↑ "Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission". SCIENCE CHINA Life Sciences. doi:10.1007/s11427-020-1637-5 (inactive 2020-01-24). Retrieved 23 January 2020.
  50. ↑ Letko, Michael; Munster, Vincent (22 January 2020). "Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV". BiorXiv. doi:10.1101/2020.01.22.915660. Retrieved 24 January 2020.
  51. ↑ Zhou, Peng; Shi, Zheng-Li (2020). "Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin". BiorXiv. doi:10.1101/2020.01.22.914952. Retrieved 24 January 2020.
  52. ↑ Gralinski, Lisa E.; Menachery, Vineet D. (2020). "Return of the Coronavirus: 2019-nCoV". Viruses. 12 (2): 135. doi:10.3390/v12020135.
  53. ↑ "上海药物所和上海科技大学联合发现一批可能对新型肺炎有治疗作用的老药和中药". Chinese Academy of Sciences. 2020-01-25.
  54. ↑ 54.0 54.1
  55. ↑ 55.0 55.1
  56. ↑ "Chinese scientists race to develop vaccine as coronavirus death toll jumps". SCMP. 2020-01-26.
  57. ↑ Cheung, Elizabeth (28 January 2020). "Hong Kong researchers have developed coronavirus vaccine, expert reveals". South China Morning Post.
  58. ↑ 58.0 58.1
  59. ↑ "Saskatchewan lab joins global effort to develop coronavirus vaccine". ca.news.yahoo.com.

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