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Severe acute respiratory syndrome-related coronavirus | |
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Transmission electron micrograph of SARS-related coronaviruses emerging from host cells cultured in the lab | |
Virus classification | |
(unranked): | Virus |
Realm: | Riboviria |
Kingdom: | Orthornavirae |
Phylum: | Pisuviricota |
Class: | Pisoniviricetes |
Order: | Nidovirales |
Family: | Coronaviridae |
Genus: | Betacoronavirus |
Subgenus: | Sarbecovirus |
Species: | Severe acute respiratory syndrome-related coronavirus
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Strains | |
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Synonyms | |
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Severe-acute-respiratory-syndrome–related coronavirus (SARSr-CoV or SARS-CoV)[note 1] is a species of virus consisting of many known strains. Two strains of the virus have caused outbreaks of severe respiratory diseases in humans: severe acute respiratory syndrome coronavirus 1 (SARS-CoV or SARS-CoV-1), which caused the 2002–2004 outbreak of severe acute respiratory syndrome (SARS), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is causing the ongoing pandemic of COVID-19.[2][3] There are hundreds of other strains of SARSr-CoV, which are only known to infect non-human mammal species: bats are a major reservoir of many strains of SARSr-CoV; several strains have been identified in Himalayan palm civets, which were likely ancestors of SARS-CoV-1.[2][4][5][6]
These enveloped, positive-sense single-stranded RNA viruses enter host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor.[7] The SARSr-CoV species is a member of the genus Betacoronavirus and the only species of the subgenus Sarbecovirus (SARS Betacoronavirus).[8][9]
The SARS-related coronavirus was one of several viruses identified by the World Health Organization (WHO) in 2016 as a likely cause of a future epidemic in a new plan developed after the Ebola epidemic for urgent research and development before and during an epidemic towards diagnostic tests, vaccines and medicines. This prediction came to pass with the COVID-19 pandemic.[10][11]
Classification
SARS-related coronavirus is a member of the genus Betacoronavirus (group 2) and monotypic of the subgenus Sarbecovirus (subgroup B).[12] Sarbecoviruses, unlike embecoviruses or alphacoronaviruses, have only one papain-like proteinase (PLpro) instead of two in the open reading frame ORF1ab.[13] SARSr-CoV was determined to be an early split-off from the betacoronaviruses based on a set of conserved domains that it shares with the group.[14][15]
Bats serve as the main host reservoir species for the SARS-related coronaviruses like SARS-CoV-1 and SARS-CoV-2. The virus has coevolved in the bat host reservoir over a long period of time.[16] Only recently have strains of SARS-related coronavirus been observed to have evolved into having been able to make the cross-species jump from bats to humans, as in the case of the strains SARS-CoV-1 and SARS-CoV-2.[17][7] Both of these strains descended from a single ancestor but made the cross-species jump into humans separately. SARS-CoV-2 is not a direct descendant of SARS-CoV-1.[2]
Genome
The SARS-related coronavirus is an enveloped, positive-sense, single-stranded RNA virus. Its genome is about 30 kb, which is one of the largest among RNA viruses. The virus has 14 open reading frames which overlap in some cases.[18] The genome has the usual 5′ methylated cap and a 3′ polyadenylated tail.[19] There are 265 nucleotides in the 5'UTR and 342 nucleotides in the 3'UTR.[18]
The 5' methylated cap and 3' polyadenylated tail allows the positive-sense RNA genome to be directly translated by the host cell's ribosome on viral entry.[20] SARSr-CoV is similar to other coronaviruses in that its genome expression starts with translation by the host cell's ribosomes of its initial two large overlapping open reading frames (ORFs), 1a and 1b, both of which produce polyproteins.[18]
Function of SARSr-CoV genome proteins | |
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Protein | Function[21][22][23][24] |
ORF1ab P0C6X7 |
Replicase/transcriptase polyprotein (pp1ab) (nonstructural proteins) |
ORF2 P59594 |
Spike (S) protein, virus binding and entry (structural protein) |
ORF3a P59632 |
Interacts with S, E, M structural proteins; Ion channel activity; Upregulates cytokines and chemokines such as IL-8 and RANTES; Upregulates NF-κB and JNK; Induces apoptosis and cell cycle arrest, via Caspase 8 and -9, and by Bax, p53, and p38 MAP kinase |
ORF3b P59633 |
Upregulates cytokines and chemokines by RUNX1b; Inhibits Type I IFN production and signaling; Induces apoptosis and cell cycle arrest; |
ORF3c P0DTG1 |
Unknown; first identified in SARS-CoV-2 but also present in SARS-CoV |
ORF3d P0DTG0 |
Novel gene in SARS-CoV-2, of unknown function |
ORF4 P59637 |
Envelope (E) protein, virus assembly and budding (structural protein) |
ORF5 P59596 |
Membrane (M) protein, virus assembly and budding (structural protein) |
ORF6 P59634 |
Enhances cellular DNA synthesis; Inhibits Type I IFN production and signaling |
ORF7a P59635 |
Inhibits cellular protein synthesis; Induces inflammatory response by NF-kappaB and IL-8 promotor; Upregulate chemokines such as IL-8 and RANTES; Upregulates JNK, p38 MAP kinase; Induces apoptosis and cell cycle arrest |
ORF7b Q7TFA1 |
Unknown |
ORF8a Q7TFA0 |
Induces apoptosis through mitochondria pathway |
ORF8b Q80H93 |
Enhances cellular DNA synthesis, also known as X5. |
ORF9a P59595 |
Nucleocapsid (N) protein, viral RNA packaging (structural protein) |
ORF9b P59636 |
Induces apoptosis |
ORF9c Q7TLC7 |
Also known as ORF14; function unknown and may not be protein-coding |
ORF10 A0A663DJA2 |
Novel gene in SARS-CoV-2, of unknown function; may not be protein-coding |
UniProt identifiers shown for SARS-CoV proteins unless they are specific to SARS-CoV-2 |
The functions of several of the viral proteins are known.[25] ORFs 1a and 1b encode the replicase/transcriptase polyprotein, and later ORFs 2, 4, 5, and 9a encode, respectively, the four major structural proteins: spike (S), envelope (E), membrane (M), and nucleocapsid (N).[26] The later ORFs also encode for eight unique proteins (orf3a to orf9b), known as the accessory proteins, many with no known homologues. The different functions of the accessory proteins are not well understood.[25]
SARS coronaviruses have been genetically engineered in several laboratories.[27]
Phylogenetics
Phylogenetic analysis showed that the evolutionary branch composed of Bat coronavirus BtKY72 and BM48-31 was the base group of SARS–related CoVs evolutionary tree, which separated from other SARS–related CoVs earlier than SARS-CoV-1 and SARS-CoV-2.[28][2]
SARSr‑CoV |
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A phylogenetic tree based on whole-genome sequences of SARS-CoV-1 and related coronaviruses is: