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2019-nCoV

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),[1][2] formerly known as the 2019 novel coronavirus (2019-nCoV),[3][4] is a positive-sense single-stranded RNA virus.[5][6][7] It is contagious among humans and is the cause of coronavirus disease 2019 (COVID-19).[8]

SARS-CoV-2 has strong genetic similarity to known bat coronaviruses, making a zoonotic origin in bats likely,[9][10][11] although an intermediate reservoir such as a pangolin is thought to be involved.[12][13] From a taxonomic perspective SARS-CoV-2 is classified as a strain of the species severe acute respiratory syndrome-related coronavirus.[1]

SARS-CoV-2 is the cause of the ongoing 2019–20 coronavirus outbreak, a Public Health Emergency of International Concern that originated in Wuhan, China.[14] Because of this connection, the virus is sometimes referred to informally, among other nicknames, as the "Wuhan coronavirus".[15][16]

Name

During the ongoing 2019–20 coronavirus outbreak, the World Health Organization (WHO) originally recommended use of the temporary designation "2019-nCoV" (2019 novel coronavirus) to refer to the virus. However, this led to concerns that the absence of an official name might lead to the use of prejudicial informal names, and in common parlance the virus was often referred to as "the new coronavirus", "Wuhan coronavirus", or simply "coronavirus".[17][18] Per 2015 WHO guidelines on the naming of viruses and diseases,[18][19] the International Committee on Taxonomy of Viruses (ICTV) announced that it would introduce a suitable official name for the virus.[17]

On 11 February 2020, the ICTV introduced the name "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2) to refer to the virus strain previously known as 2019-nCoV.[1] Earlier the same day, the WHO officially renamed the disease caused by the virus strain from "2019-nCoV acute respiratory disease" to coronavirus disease 2019 (COVID-19).[20][2]

Virology

Infection

Human-to-human transmission of the virus has been confirmed[8] and occurs primarily via respiratory droplets from coughs and sneezes within a range of about 6 feet (1.8 m).[21][22] Viral RNA has also been found in stool samples from infected patients.[23]

It is possible that the virus can be infectious even during the incubation period, but this has not been proven,[24] and the WHO stated on 1 February 2020 that "transmission from asymptomatic cases is likely not a major driver of transmission" at this time.[25]

Reservoir

Animals sold for food were originally suspected to be the reservoir or intermediary hosts of SARS-CoV-2 because many of the first individuals found to be infected by the virus were workers at the Huanan Seafood Market.[26] 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.[27] The outbreak has prompted a temporary ban on the trade and consumption of wild animals in China.[28][29] However, some researchers have suggested that the Huanan Seafood Market may not be the original source of viral transmission to humans.[30][31]

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. Two viral nucleic acid sequences from Rhinolophus sinicus published in 2015 and 2017 show a resemblance of 80% to SARS-CoV-2.[32][33][11] A third viral nucleic acid sequence from Rhinolophus affinis, "RaTG13" collected in Yunnan province, has a 96% resemblance to SARS-CoV-2.[9][34] 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.[35]

Researchers from Guangzhou claim to have found a "99% identical" viral nucleic acid sequence in a pangolin sample.[36] As of 12 February 2020, the sequence remains unavailable, and all information comes from a university announcement.[37] Pangolins are protected under Chinese law, but poaching and trading of pangolins for traditional medicine remains common. A metagenomic study published in 2019 previously revealed that SARS-CoV was the most widely distributed coronavirus among a sample of Malayan pangolins.[38] Microbiologists and geneticists in Texas have independently found evidence of recombination in coronaviruses suggesting pangolin origins of SARS-CoV-2; they acknowledged remaining unknown factors while urging continued examination of other mammals.[39]

Phylogenetics and taxonomy

Genomic information
2019-nCoV genome.svg
Genomic organisation of SARS-CoV-2
NCBI genome IDMN908947
Genome size29,903 bases
Year of completion2020

SARS-CoV-2 belongs to the broad family of viruses known as coronaviruses. 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). It is the seventh known coronavirus to infect people, after 229E, NL63, OC43, HKU1, MERS-CoV, and the original SARS-CoV.[40]

Like the SARS-related coronavirus strain implicated in the 2003 SARS outbreak, SARS-CoV-2 is a member of the subgenus Sarbecovirus (Beta-CoV lineage B).[41][26][42] Its RNA sequence is approximately 30,000 bases in length.[7]

With a sufficient number of sequenced genomes, it is possible to reconstruct a phylogenetic tree of the mutation history of a family of viruses. By 12 January 2020, five genomes of SARS-CoV-2 had been isolated from Wuhan and reported by the Chinese Center for Disease Control and Prevention (CCDC) and other institutions;[7][43] the number of genomes increased to 81 by 11 February 2020.[44] A phylogenic analysis of the samples shows they are "highly related with at most seven mutations relative to a common ancestor", implying that the first human infection occurred in November or December 2019.[44]

On 11 February 2020, ICTV announced that according to existing rules that compute hierarchical relationships among coronaviruses on the basis of five conserved sequences of nucleic acids, the differences between what was then called 2019-nCoV and the virus strain from the 2003 SARS outbreak were insufficient to make it a separate viral species. Therefore, they identified 2019-nCoV as a strain of severe acute respiratory syndrome-related coronavirus.[1]

Structural biology

Ribbon diagram of M(pro) protease, a prospective target for antiviral drugs against SARS-CoV-2
Ribbon diagram of M(pro) protease, a prospective target for antiviral drugs against SARS-CoV-2

Protein modeling experiments on the spike (S) protein of the virus suggest that it has sufficient affinity to the angiotensin converting enzyme 2 (ACE2) receptors of human cells to use them as a mechanism of cell entry.[45] On 22 January 2020, a group in China working with the full virus genome and a group in the United States using reverse genetics methods independently and experimentally demonstrated that ACE2 could act as the receptor for SARS-CoV-2.[46][47][48][49] Studies have shown that SARS-CoV-2 has a higher affinity to human ACE2 than the original SARS virus strain.[50] An atomic-level image of the S protein has been created using cryogenic electron microscopy.[51][52]

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,[53] and the Chinese Academy of Sciences has produced an unpublished experimental structure of a recombinant 2019-nCoV protease.[54] In addition, researchers have modeled the structures of all mature peptides in the SARS-CoV-2 genome using I-TASSER and Swiss-model.[55][56]

Epidemiology

The first known human infection by the strain occurred in early December 2019.[57][30] Proliferation of SARS-CoV-2 was first detected in Wuhan, China, in mid-December 2019, likely originating from a single infected animal.[30] The virus subsequently spread to all provinces of China and to more than two dozen other countries in Asia, Europe, North America, Africa, and Oceania.[58] Human-to-human spread of the virus has been confirmed in all of these regions[8][59][60][61] except Africa.[62] On 30 January 2020, 2019-nCoV was designated a Public Health Emergency of International Concern by the WHO.[14][63]

As of 20 February 2020 (15:30 UTC), there were 75,752 confirmed cases of infection, of which 74,579 were within mainland China.[58] One mathematical model estimated the number of people infected in Wuhan alone at 75,815 as of 25 January 2020.[64] 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.[65][66] While the proportion of infections that result in confirmed infection or progress to diagnosable disease remains unclear,[67][68] the total number of deaths attributed to the virus was 2,130 as of 20 February 2020 (15:30 UTC); over 95% of all deaths have occurred in Hubei province,[58] where Wuhan is located.

The basic reproduction number (, pronounced R-nought or R-zero)[69] of the virus has been estimated to be between 1.4 and 3.9.[70][71][72][73] 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.[74]

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Further reading

  • World Health Organization (2020). Laboratory testing of human suspected cases of novel coronavirus (nCoV) infection: interim guidance, 10 January 2020 (Report). World Health Organization. hdl:10665/330374. WHO/2019-nCoV/laboratory/2020.1.
  • World Health Organization (2020). WHO R&D Blueprint: informal consultation on prioritization of candidate therapeutic agents for use in novel coronavirus 2019 infection, Geneva, Switzerland, 24 January 2020 (Report). World Health Organization. hdl:10665/330680. WHO/HEO/R&D Blueprint (nCoV)/2020.1.
  • Habibzadeh, Parham; Stoneman, Emily K. (February 2020). "The Novel Coronavirus: A Bird's Eye View". Int J Occup Environ Med. 11 (2): 65–71. doi:10.15171/ijoem.2020.1921. PMID 32020915.

External links

Classification