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2019-nCoV belongs to the broad family of viruses known as [[coronavirus]]es; "[[nCoV]]" is the standard term used to refer to novel coronaviruses until the choice of a more specific designation. It is a [[positive-sense single-stranded RNA virus|positive-sense single-stranded RNA]] (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the [[common cold]] to more severe diseases such as [[Middle East respiratory syndrome]] (MERS) and [[Severe acute respiratory syndrome]] (SARS). It is the seventh known coronavirus to infect people, after [[Human coronavirus 229E|229E]], [[Human coronavirus NL63|NL63]], [[Human coronavirus OC43|OC43]], [[Human coronavirus HKU1|HKU1]], [[Middle East respiratory syndrome-related coronavirus|MERS-CoV]], and [[Severe acute respiratory syndrome-related coronavirus|SARS-CoV]].<ref name="NEJM">{{cite journal |last1=Zhu |first1=Na |last2=Zhang |first2=Dingyu |last3=Wang |first3=Wenling |last4=Li |first4=Xinwang |last5=Yang |first5=Bo |last6=Song |first6=Jingdong |last7=Zhao |first7=Xiang |last8=Huang |first8=Baoying |last9=Shi |first9=Weifeng |last10=Lu |first10=Roujian |last11=Niu |first11=Peihua |last12=Zhan |first12=Faxian |last13=Ma |first13=Xuejun |last14=Wang |first14=Dayan |last15=Xu |first15=Wenbo |last16=Wu |first16=Guizhen |last17=Gao |first17=George F. |last18=Tan |first18=Wenjie |title=A Novel Coronavirus from Patients with Pneumonia in China, 2019 |journal=[[New England Journal of Medicine]] |location=United States |date=24 January 2020 |volume=0 |doi=10.1056/NEJMoa2001017 |pmid=31978945 |issn=0028-4793}}<!--Location refers to where the publisher is from.--></ref>
2019-nCoV belongs to the broad family of viruses known as [[coronavirus]]es; "[[nCoV]]" is the standard term used to refer to novel coronaviruses until the choice of a more specific designation. It is a [[positive-sense single-stranded RNA virus|positive-sense single-stranded RNA]] (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the [[common cold]] to more severe diseases such as [[Middle East respiratory syndrome]] (MERS) and [[Severe acute respiratory syndrome]] (SARS). It is the seventh known coronavirus to infect people, after [[Human coronavirus 229E|229E]], [[Human coronavirus NL63|NL63]], [[Human coronavirus OC43|OC43]], [[Human coronavirus HKU1|HKU1]], [[Middle East respiratory syndrome-related coronavirus|MERS-CoV]], and [[Severe acute respiratory syndrome-related coronavirus|SARS-CoV]].<ref name="NEJM">{{cite journal |last1=Zhu |first1=Na |last2=Zhang |first2=Dingyu |last3=Wang |first3=Wenling |last4=Li |first4=Xinwang |last5=Yang |first5=Bo |last6=Song |first6=Jingdong |last7=Zhao |first7=Xiang |last8=Huang |first8=Baoying |last9=Shi |first9=Weifeng |last10=Lu |first10=Roujian |last11=Niu |first11=Peihua |last12=Zhan |first12=Faxian |last13=Ma |first13=Xuejun |last14=Wang |first14=Dayan |last15=Xu |first15=Wenbo |last16=Wu |first16=Guizhen |last17=Gao |first17=George F. |last18=Tan |first18=Wenjie |title=A Novel Coronavirus from Patients with Pneumonia in China, 2019 |journal=[[New England Journal of Medicine]] |location=United States |date=24 January 2020 |volume=0 |doi=10.1056/NEJMoa2001017 |pmid=31978945 |issn=0028-4793}}<!--Location refers to where the publisher is from.--></ref>


Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus ''[[Sarbecovirus]]'' (Beta-CoV lineage B).<ref>{{cite web |url=https://nextstrain.org/groups/blab/sars-like-cov |title=Phylogeny of SARS-like betacoronaviruses |website=nextstrain |accessdate=18 January 2020 |archive-url=https://web.archive.org/web/20200120190511/https://nextstrain.org/groups/blab/sars-like-cov |archive-date=20 January 2020 |url-status=live }}</ref><ref name="Hui14Jan2020" /><ref name="Wong2019">{{vcite journal |authors=Antonio C. P. Wong, Xin Li, Susanna K. P. Lau, Patrick C. Y. Woo |pmc=6409556 |title=Global Epidemiology of Bat Coronaviruses |journal=Viruses |year=2019 Feb |volume=11 |issue=2 |pages=174 |doi=10.3390/v11020174}}</ref><ref name="Randhawa2020">{{cite journal |last1=Randhawa |first1=Gurjit S. |last2=Soltysiak |first2=Maximillian P. M. |last3=Roz |first3=Hadi El |last4=Souza |first4=Camila P. E. de |last5=Hill |first5=Kathleen A. |last6=Kari |first6=Lila |title=Machine learning-based analysis of genomes suggests associations between Wuhan 2019-nCoV and bat Betacoronaviruses |journal=bioRxiv |date=4 February 2020 |pages=2020.02.03.932350 |doi=10.1101/2020.02.03.932350 |language=en}}</ref>. Its [[RNA]] sequence is approximately 30,000 [[nucleobase|base]]s in length.<ref name=":gisaid"/>
Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus ''[[Sarbecovirus]]'' (Beta-CoV lineage B).<ref>{{cite web |url=https://nextstrain.org/groups/blab/sars-like-cov |title=Phylogeny of SARS-like betacoronaviruses |website=nextstrain |accessdate=18 January 2020 |archive-url=https://web.archive.org/web/20200120190511/https://nextstrain.org/groups/blab/sars-like-cov |archive-date=20 January 2020 |url-status=live }}</ref><ref name="Hui14Jan2020" /><ref name="Wong2019">{{vcite journal |authors=Antonio C. P. Wong, Xin Li, Susanna K. P. Lau, Patrick C. Y. Woo |pmc=6409556 |title=Global Epidemiology of Bat Coronaviruses |journal=Viruses |year=2019 Feb |volume=11 |issue=2 |pages=174 |doi=10.3390/v11020174}}</ref> Its [[RNA]] sequence is approximately 30,000 [[nucleobase|base]]s in length.<ref name=":gisaid"/>


By 12 January, five genomes of 2019-nCoV had been isolated from Wuhan and reported by the [[Chinese Center for Disease Control and Prevention]] (CCDC) and other institutions;<ref name=":gisaid"/><ref>{{cite web |url=http://virological.org/t/initial-genome-release-of-novel-coronavirus/319 |title=Initial genome release of novel coronavirus |date=11 January 2020 |website=Virological |accessdate=12 January 2020 |archive-url=https://web.archive.org/web/20200112100227/http://virological.org/t/initial-genome-release-of-novel-coronavirus/319 |archive-date=12 January 2020 |url-status=live }}</ref><ref>{{Cite journal |date=17 January 2020 |title=Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome |url= http://www.ncbi.nlm.nih.gov/nuccore/MN908947.3 |journal=[[National Center for Biotechnology Information]] |publisher=National Institutes of Health |location=United States}}</ref> the number of genomes increased to 28 by 26 January.{{citation needed|date=February 2020}} Except for the earliest GenBank genome, the genomes are under an embargo at [[GISAID]]. A phylogenic analysis for the samples is available through Nextstrain.<ref>{{cite web|url=https://nextstrain.org/ncov|title=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|last1=Bedford|first1=Trevor|last2=Neher|first2=Richard|date=|website=nextstrain.org|url-status=live|archive-url=|archive-date=|accessdate=26 January 2020}}</ref>
By 12 January, five genomes of 2019-nCoV had been isolated from Wuhan and reported by the [[Chinese Center for Disease Control and Prevention]] (CCDC) and other institutions;<ref name=":gisaid"/><ref>{{cite web |url=http://virological.org/t/initial-genome-release-of-novel-coronavirus/319 |title=Initial genome release of novel coronavirus |date=11 January 2020 |website=Virological |accessdate=12 January 2020 |archive-url=https://web.archive.org/web/20200112100227/http://virological.org/t/initial-genome-release-of-novel-coronavirus/319 |archive-date=12 January 2020 |url-status=live }}</ref><ref>{{Cite journal |date=17 January 2020 |title=Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome |url= http://www.ncbi.nlm.nih.gov/nuccore/MN908947.3 |journal=[[National Center for Biotechnology Information]] |publisher=National Institutes of Health |location=United States}}</ref> the number of genomes increased to 28 by 26 January.{{citation needed|date=February 2020}} Except for the earliest GenBank genome, the genomes are under an embargo at [[GISAID]]. A phylogenic analysis for the samples is available through Nextstrain.<ref>{{cite web|url=https://nextstrain.org/ncov|title=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|last1=Bedford|first1=Trevor|last2=Neher|first2=Richard|date=|website=nextstrain.org|url-status=live|archive-url=|archive-date=|accessdate=26 January 2020}}</ref>

Revision as of 03:56, 6 February 2020

2019-nCoV
Illustration of a 2019-nCoV virion
Illustration of a 2019-nCoV virion
Cross-sectional illustration of 2019-nCoV virions showing internal components
Cross-sectional illustration of 2019-nCoV virions showing internal components
Virus classification Edit this classification
(unranked): Virus
Realm: Riboviria
Kingdom: Orthornavirae
Phylum: Pisuviricota
Class: Pisoniviricetes
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Virus:
2019-nCoV
SARS-CoV-2 is located in China
SARS-CoV-2
Wuhan, China, the epicenter of the only recorded outbreak
Synonyms

The 2019 novel coronavirus (provisionally named 2019-nCoV),[3][4] informally known as the Wuhan coronavirus,[5] is a contagious virus that causes the respiratory infection 2019-nCoV acute respiratory disease. It is the cause of the ongoing 2019–20 Wuhan coronavirus outbreak.[6] Genomic sequencing has shown that it is a positive-sense, single-stranded RNA coronavirus.[7][8][9]

Many early cases were linked to a large seafood and animal market, and the virus is thought to have a zoonotic origin.[10][11] Comparisons of the genetic sequences of this virus and other virus samples have shown similarities to SARS-CoV (79.5%)[12] and bat coronaviruses (96%),[12] which makes an ultimate origin in bats likely.[13][14]

Epidemiology

The first known human infection occurred in early December 2019.[15][16] An outbreak of 2019-nCoV was first detected in Wuhan, China, in mid-December 2019, likely originating from a single infected animal.[16] The virus subsequently spread to all provinces of China and to more than two dozen other countries in Asia, Europe, North America, and Oceania.[17] Human-to-human spread of the virus has been confirmed in all of these regions.[18][19][20][21]

On 30 January 2020, 2019-nCoV was designated a global health emergency by the World Health Organization (WHO).[22][23][24] As of 5 February 2020 (15:30 UTC), there were 24,604 confirmed cases of infection, of which 24,391 were within mainland China.[17] To date, approximately one-fifth of diagnosed cases result in serious illness.[25] Nearly all cases outside China have occurred in people who either traveled from Wuhan, or were in direct contact with someone who traveled from the area.[26][27]

Overall mortality and morbidity rates due to infection from 2019-nCoV are unknown, both because the case fatality rate may be changing over time in the current outbreak, and because the number of minor and asymptomatic cases not resulting in diagnosis remains unclear.[28][29] However, preliminary research resulted in 2.9% and 14.6% mortality numbers.[30][31] The WHO has suggested that the case fatality rate is approximately 3%.[32] The total number of deaths attributed to the virus was 494 as of 5 February 2020 (15:30 UTC), almost all in Hubei province.[17]

Virology

Infection

Human-to-human transmission of the virus has been confirmed.[18] Coronaviruses are primarily spread through close contact, in particular through respiratory droplets from coughs and sneezes within a range of about 6 feet (1.8 m).[33][34] Viral RNA has also been found in stool samples from infected patients.[35] It is possible that the virus can be infectious even during the incubation period, but this has not been proven,[36] and the WHO states that "transmission from asymptomatic cases is likely not a major driver of transmission" at this time.[37]

The basic reproduction number (, pronounced R-nought or R-zero)[38] of the virus has been estimated to be between 1.4 and 3.9.[39][40][41][42][43] This means that, when unchecked, the virus typically results in 1.4 to 3.9 new cases per established infection. It has been established that the virus is able to transmit along a chain of at least four people.[44]

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.[45] A market selling live animals for food was also blamed in the SARS outbreak in 2003; such markets are considered to be incubators for novel pathogens.[46] The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.[47] However, some researchers have suggested that the Huanan Seafood Market may not be the original source of viral transmission to humans.[16][48]

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. Research into the origin of the 2003 SARS outbreak has resulted in the discovery of many SARS-like bat coronaviruses, most originating in the Rhinolophus genus of horseshoe bats. 2019-nCoV falls 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.[49][13] A third virus genome from Rhinolophus affinis, "RaTG13" collected in Yunnan province, has a 96% resemblance to 2019-nCoV.[50][51] For comparison, this amount of variation among viruses is similar to the amount of mutation observed over ten years in the H3N2 human influenza virus strain.[52]

Phylogenetics and taxonomy

Genomic information
Genomic organisation of 2019-nCoV
NCBI genome IDMN908947
Genome size29,903 bases
Year of completion2020

2019-nCoV belongs to the broad family of viruses known as coronaviruses; "nCoV" is the standard term used to refer to novel coronaviruses until the choice of a more specific designation. It is a positive-sense single-stranded RNA (+ssRNA) virus. Other coronaviruses are capable of causing illnesses ranging from the common cold to more severe diseases such as 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.[53]

Though genetically distinct from other coronaviruses that infect humans, it is, like SARS-CoV, a member of the subgenus Sarbecovirus (Beta-CoV lineage B).[54][45][55] Its RNA sequence is approximately 30,000 bases in length.[9]

By 12 January, five genomes of 2019-nCoV had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions;[9][56][57] the number of genomes increased to 28 by 26 January.[citation needed] Except for the earliest GenBank genome, the genomes are under an embargo at GISAID. A phylogenic analysis for the samples is available through Nextstrain.[58]

Structural biology

Ribbon diagram of M(pro) protease], a prospective target for antiviral drugs against 2019-nCoV
Ribbon diagram of M(pro) protease, a prospective target for antiviral drugs against 2019-nCoV

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.[59] 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.[60][61][62]

To look for potential protease inhibitors, the viral 3C-like protease M(pro) from the ORF1a polyprotein has also been modeled for drug docking experiments. Innophore has produced two computational models based on SARS protease,[63] and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.[64] In addition, researchers at the University of Michigan have modeled the structures of all mature peptides in the 2019-nCov genome using I-TASSER.[65]

Vaccine research

In January 2020, several organizations and institutions began work on creating vaccines for 2019-nCoV based on the published genome.[66]

In China, the Chinese Center for Disease Control and Prevention is developing a vaccine against the novel coronavirus.[67][68] 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.[69] Shanghai East Hospital is also developing a vaccine in partnership with the biotechnology company Stemirna Therapeutics.[70]

Elsewhere, three vaccine projects are being supported by the Coalition for Epidemic Preparedness Innovations (CEPI), including projects by the biotechnology companies Moderna and Inovio Pharmaceuticals and another by the University of Queensland.[71] 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.[66] Inovio Pharmaceuticals is developing a DNA-based vaccination and collaborating with a Chinese firm in order to speed its acceptance by regulatory authorities in China, hoping to perform human trials of the vaccine in the summer of 2020.[72] 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.[71]

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.[73] VIDO-InterVac aims to start production and animal testing in March 2020, and human testing in 2021.[74]

The Imperial College Faculty of Medicine in London has funding to develop a vaccine and take it to animal testing, a phase of research it expects to complete by mid-February 2020.[75]

Name

Until February, the virus was not afforded a distinct name. It was reported as 'the coronavirus' or 'the new coronavirus', while the WHO recommended the temporary title '2019-nCoV'. Amid concerns that the absence of an official name could allow the rise of popular terms prejudicial against certain populations, animals or locations, in late January, the International Committee on Taxonomy of Viruses (ICTV) decided on a name, which it was due to announce in the second week of February.[76]

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Further reading

Open access preprint repositories

(Suggested search term: "2019-nCoV")

  • "bioRxiv". The preprint server for biology (bioRxiv).
  • "medRxiv". The preprint server for health sciences.
  • "SSRN". Rapid worldwide dissemination of research.