View source for SARS-related coronavirus

{{Short description|Species of coronavirus causing SARS and COVID-19}}
{{about|a species of coronavirus comprising multiple strains|the strain that causes SARS|SARS-CoV-1|the strain that causes COVID-19|SARS-CoV-2}}
{{Use Oxford spelling|date=August 2022}}
{{Use dmy dates|date=May 2025}}
{{Virusbox
| name              = SARS-related coronavirus
| image             = SARS-CoV with corona.jpg
| image_caption     = [[Transmission electron micrograph]] of SARS-related coronaviruses emerging from [[host cell]]s cultured in the lab
| parent            = Sarbecovirus
| species           = Betacoronavirus pandemicum
| synonyms          =
* ''SARS coronavirus''
* ''SARS-related coronavirus''
* ''Severe acute respiratory syndrome coronavirus''<ref name="TaxHist">{{cite web |title=ICTV Taxonomy history: ''Severe acute respiratory syndrome-related coronavirus'' |url=https://ictv.global/taxonomy/taxondetails?taxnode_id=20181868 |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=27 January 2019 |language=en }}</ref>
| synonyms_ref      =
| subdivision_ranks = Strains
| subdivision       =
* [[Severe acute respiratory syndrome coronavirus 1|SARS-CoV-1]]
* [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]]
* [[Bat SARS-like coronavirus WIV1]]
* [[RaTG13|Bat coronavirus RaTG13]]
* Numerous other bat-hosted strains
}}

'''Severe acute respiratory syndrome–related coronavirus''' ('''SARSr-CoV''' or '''SARS-CoV''''', '''Betacoronavirus pandemicum''''')<ref>{{cite web |title=Taxon Details {{!}} ICTV |url=https://ictv.global/taxonomy/taxondetails?taxnode_id=202301868&taxon_name=Betacoronavirus%20pandemicum |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=30 May 2024}}</ref><ref group=note>The terms ''SARSr-CoV'' and ''SARS-CoV'' are sometimes used interchangeably, especially prior to the discovery of SARS-CoV-2. This may cause confusion when some publications refer to SARS-CoV-1 as ''SARS-CoV''.</ref> is a [[species]] of virus consisting of many known [[Strain (biology)|strains]]. Two strains of the virus have caused [[Disease outbreak|outbreaks]] of severe [[respiratory diseases]] in humans: [[severe acute respiratory syndrome coronavirus 1]] (SARS-CoV or SARS-CoV-1), the cause of [[2002–2004 SARS outbreak|the 2002–2004 outbreak]] of [[severe acute respiratory syndrome]] (SARS), and [[severe acute respiratory syndrome coronavirus 2]] (SARS-CoV-2), the cause of [[COVID-19 pandemic|the pandemic]] of [[coronavirus disease 2019|COVID-19]].<ref name="CVSG">{{cite journal | title = The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 | journal = Nature Microbiology | date = March 2020 | pmid = 32123347 | doi = 10.1038/s41564-020-0695-z | author1 = Coronaviridae Study Group of the International Committee on Taxonomy of Viruses | volume = 5 | issue = 4 | pages = 536–544 | pmc = 7095448 | doi-access = free }}</ref><ref name="SCI">{{cite journal |last1=Kohen |first1=Jon |last2=Kupferschmidth |first2=Kai |title=Strategies shift as coronavirus pandemic looms |journal=Science |date=28 February 2020 |volume=367 |issue=6481 |pages=962–963 |doi=10.1126/science.367.6481.962 |pmid=32108093 |bibcode=2020Sci...367..962C |s2cid=211556915 |doi-access= }}</ref> There are hundreds of other strains of SARSr-CoV, which are only known to infect non-human mammal species: [[Bat virome|bats are a major reservoir]] of many strains of SARSr-CoV; several strains have been identified in [[Himalayan palm civet]]s, which were likely ancestors of SARS-CoV-1.<ref name="CVSG" /><ref>{{cite journal | vauthors = Lau SK, Li KS, Huang Y, Shek CT, Tse H, Wang M, Choi GK, Xu H, Lam CS, Guo R, Chan KH, Zheng BJ, Woo PC, Yuen KY | display-authors = 6 | title = Ecoepidemiology and complete genome comparison of different strains of severe acute respiratory syndrome-related Rhinolophus bat coronavirus in China reveal bats as a reservoir for acute, self-limiting infection that allows recombination events | journal = Journal of Virology | volume = 84 | issue = 6 | pages = 2808–19 | date = March 2010 | pmid = 20071579 | pmc = 2826035 | doi = 10.1128/JVI.02219-09 | doi-access = free }}</ref><ref>{{Cite news |last=Branswell |first=Helen | name-list-style = vanc |url=https://www.statnews.com/2015/11/09/sars-like-virus-bats-shows-potential-infect-humans-study-finds/|title=SARS-like virus in bats shows potential to infect humans, study finds|date=9 November 2015|work=Stat News|access-date=20 February 2020}}</ref><ref>{{cite journal | vauthors = Wong AC, Li X, Lau SK, Woo PC | title = Global Epidemiology of Bat Coronaviruses | journal = Viruses | volume = 11 | issue = 2 | page = 174 | date = February 2019 | pmid = 30791586 | pmc = 6409556 | doi = 10.3390/v11020174 | quote = Most notably, horseshoe bats were found to be the reservoir of SARS-like CoVs, while palm civet cats are considered to be the intermediate host for SARS-CoVs [43,44,45]. | doi-access = free }}</ref>

These [[viral envelope|enveloped]], [[positive-sense single-stranded RNA virus]]es enter host cells by binding to the [[angiotensin-converting enzyme 2]] (ACE2) receptor.<ref name="pmid24172901"/> The SARSr-CoV species is a member of the genus ''[[Betacoronavirus]]'' and the only species of the subgenus '''''Sarbecovirus''''' ('''SAR'''S '''Be'''ta'''co'''rona'''virus''').<ref name="ICTV10">{{cite web |title=Virus Taxonomy: 2018 Release |url=https://ictv.global/taxonomy |website=International Committee on Taxonomy of Viruses (ICTV) |access-date=13 January 2019 |language=en |date=October 2018}}</ref><ref name=":02">{{cite journal | vauthors = Woo PC, Huang Y, Lau SK, Yuen KY | title = Coronavirus genomics and bioinformatics analysis | journal = Viruses | volume = 2 | issue = 8 | pages = 1804–20 | date = August 2010 | pmid = 21994708 | pmc = 3185738 | doi = 10.3390/v2081803 | quote = Figure 2. Phylogenetic analysis of RNA-dependent RNA polymerases (Pol) of coronaviruses with complete genome sequences available. The tree was constructed by the neighbor-joining method and rooted using Breda virus polyprotein. | doi-access = free }}</ref>

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 [[Western African Ebola virus epidemic|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]].<ref>{{cite web|last1=Kieny|first1=Marie-Paule | name-list-style = vanc |title=After Ebola, a Blueprint Emerges to Jump-Start R&D|url=https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|website=Scientific American Blog Network|access-date=13 December 2016|url-status=live|archive-url=https://web.archive.org/web/20161220134725/https://blogs.scientificamerican.com/guest-blog/after-ebola-a-blueprint-emerges-to-jump-start-r-d/|archive-date=20 December 2016}}</ref><ref>{{cite web|title=LIST OF PATHOGENS|url=https://www.who.int/csr/research-and-development/list_of_pathogens/en/|website=World Health Organization|access-date=13 December 2016|url-status=dead|archive-url=https://web.archive.org/web/20161220180509/http://www.who.int/csr/research-and-development/list_of_pathogens/en/|archive-date=20 December 2016}}</ref>

== Classification ==
SARS-related coronavirus is a member of the genus ''[[Betacoronavirus]]'' (group 2) and [[Monotypic taxon|monotypic]] of the subgenus ''Sarbecovirus'' (subgroup B).<ref>{{cite journal | vauthors = Wong AC, Li X, Lau SK, Woo PC | title = Global Epidemiology of Bat Coronaviruses | journal = Viruses | volume = 11 | issue = 2 | page = 174 | date = February 2019 | pmid = 30791586 | pmc = 6409556 | doi = 10.3390/v11020174 | quote = See Figure 1. | doi-access = free }}</ref>  Sarbecoviruses, unlike [[embecovirus]]es or [[alphacoronavirus]]es, have only one [[papain-like proteinase]] (PLpro) instead of two in the [[open reading frame]] [[ORF1ab]].<ref>{{cite journal | vauthors = Woo PC, Huang Y, Lau SK, Yuen KY | title = Coronavirus genomics and bioinformatics analysis | journal = Viruses | volume = 2 | issue = 8 | pages = 1804–20 | date = August 2010 | pmid = 21994708 | pmc = 3185738 | doi = 10.3390/v2081803 | quote = See Figure 1. | doi-access = free }}</ref> 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.<ref>{{cite journal | vauthors = Woo PC, Huang Y, Lau SK, Yuen KY | title = Coronavirus genomics and bioinformatics analysis | journal = Viruses | volume = 2 | issue = 8 | pages = 1804–20 | date = August 2010 | pmid = 21994708 | pmc = 3185738 | doi = 10.3390/v2081803 | quote = Furthermore, subsequent phylogenetic analysis using both complete genome sequence and proteomic approaches, it was concluded that SARSr-CoV is probably an early split-off from the Betacoronavirus lineage [1]; See Figure 2. | doi-access = free }}</ref><ref>{{cite web|url=https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/223/coronaviridae-figures|archive-url=https://wayback.archive-it.org/all/20200403193811/https://talk.ictvonline.org/ictv-reports/ictv_9th_report/positive-sense-rna-viruses-2011/w/posrna_viruses/223/coronaviridae-figures|url-status=dead|archive-date=3 April 2020|title=Coronaviridae - Figures - Positive Sense RNA Viruses - Positive Sense RNA Viruses (2011) | work = International Committee on Taxonomy of Viruses (ICTV)|language=en |access-date=6 March 2020|quote=See Figure 2.}}</ref>

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-borne virus|bat host reservoir]] over a long period of time.<ref>{{cite journal | vauthors = Gouilh MA, Puechmaille SJ, Gonzalez JP, Teeling E, Kittayapong P, Manuguerra JC | title = SARS-Coronavirus ancestor's foot-prints in South-East Asian bat colonies and the refuge theory | journal = Infection, Genetics and Evolution | volume = 11 | issue = 7 | pages = 1690–702 | date = October 2011 | pmid = 21763784 | doi = 10.1016/j.meegid.2011.06.021 | pmc = 7106191 | bibcode = 2011InfGE..11.1690G | quote = Betacoronaviruses-b ancestors, meaning SARSr-CoVs ancestors, could have been historically hosted by the common ancestor of the Rhinolophidae and Hipposideridae and could have later evolved independently in the lineages leading towards Rhinolophidae and Hipposideridae betacoronaviruses. | doi-access = free }}</ref> Only recently have strains of SARS-related coronavirus been observed to have evolved into having been able to make the [[Cross-species transmission|cross-species jump]] from bats to humans, as in the case of the strains [[Severe acute respiratory syndrome coronavirus 1|SARS-CoV-1]] and [[Severe acute respiratory syndrome coronavirus 2|SARS-CoV-2]].<ref name="pmid18258002">{{cite journal | vauthors = Cui J, Han N, Streicker D, Li G, Tang X, Shi Z, Hu Z, Zhao G, Fontanet A, Guan Y, Wang L, Jones G, Field HE, Daszak P, Zhang S | display-authors = 6 | title = Evolutionary relationships between bat coronaviruses and their hosts | journal = Emerging Infectious Diseases | volume = 13 | issue = 10 | pages = 1526–32 | date = October 2007 | pmid = 18258002 | pmc = 2851503 | doi = 10.3201/eid1310.070448 }}</ref><ref name="pmid24172901">{{cite journal | vauthors = Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, Mazet JK, Hu B, Zhang W, Peng C, Zhang YJ, Luo CM, Tan B, Wang N, Zhu Y, Crameri G, Zhang SY, Wang LF, Daszak P, Shi ZL | display-authors = 6 | title = Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor | journal = Nature | volume = 503 | issue = 7477 | pages = 535–8 | date = November 2013 | pmid = 24172901 | pmc = 5389864 | doi = 10.1038/nature12711 | bibcode = 2013Natur.503..535G }}</ref> 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.<ref name="CVSG" />

== Genome ==
[[File:SARS-CoV genome organization.jpg|thumb|[[Genome]] organization and viral [[proteins]] of [[SARS-CoV]]]]
The SARS-related [[coronavirus]] is an enveloped, [[positive-sense single-stranded RNA virus|positive-sense, single-stranded RNA virus]]. Its genome is about 30&nbsp;[[kilobase|kb]], which is one of the largest among RNA viruses. The virus has 14 [[open reading frame]]s which overlap in some cases.<ref name="Snijder_2003">{{cite journal | vauthors = Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, Guan Y, Rozanov M, Spaan WJ, Gorbalenya AE | display-authors = 6 | title = Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage | journal = Journal of Molecular Biology | volume = 331 | issue = 5 | pages = 991–1004 | date = August 2003 | pmid = 12927536 | doi = 10.1016/S0022-2836(03)00865-9 | pmc = 7159028 | quote = The SARS-CoV genome is ~29.7 kb long and contains 14 open reading frames (ORFs) flanked by 5′ and 3′-untranslated regions of 265 and 342 nucleotides, respectively (Figure 1). | doi-access = free }}</ref> The genome has the usual [[five-prime cap|5′ methylated cap]] and a [[polyadenylation|3′ polyadenylated tail]].<ref name = "Fehr_2015">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc }}</ref> There are 265 [[nucleotides]] in the [[Five prime untranslated region|5'UTR]] and 342 nucleotides in the [[Three prime untranslated region|3'UTR]].<ref name="Snijder_2003" />

The 5' methylated cap and 3' polyadenylated tail allows the [[messenger RNA|positive-sense RNA genome]] to be directly [[translation (biology)|translated]] by the host cell's [[ribosome]] on [[viral entry]].<ref>{{cite book | vauthors = Fehr AR, Perlman S | title = Coronaviruses | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | series = Methods in Molecular Biology | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc }}</ref> 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 [[polyprotein]]s.<ref name="Snijder_2003" />
{| class="wikitable mw-collapsible mw-collapsed" |col2style=text-align:right style="width:auto; float:right; clear:right; margin:0px 0px 0.5em 1em"
!colspan=2| Function of SARSr-CoV <br /> genome proteins
|-
! Protein || Function<ref name=McBride2012_Table1>{{cite journal | vauthors = McBride R, Fielding BC | title = The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis | journal = Viruses | volume = 4 | issue = 11 | pages = 2902–23 | date = November 2012 | pmid = 23202509 | pmc = 3509677 | doi = 10.3390/v4112902 |quote=See Table 1. | doi-access = free }}</ref><ref name="Tang_2009">{{cite journal | vauthors = Tang X, Li G, Vasilakis N, Zhang Y, Shi Z, Zhong Y, Wang LF, Zhang S | title = Differential stepwise evolution of SARS coronavirus functional proteins in different host species | journal = BMC Evolutionary Biology | volume = 9 | article-number = 52 | date = March 2009 | issue = 1 | pmid = 19261195 | pmc = 2676248 | doi = 10.1186/1471-2148-9-52 | doi-access = free | bibcode = 2009BMCEE...9...52T }}</ref><ref>{{Cite journal|last1=Narayanan|first1=Krishna|last2=Huang|first2=Cheng|last3=Makino|first3=Shinji|date=April 2008|title=SARS coronavirus Accessory Proteins|journal=Virus Research|volume=133|issue=1|pages=113–121|doi=10.1016/j.virusres.2007.10.009|issn=0168-1702|pmc=2720074|pmid=18045721|quote=See Table 1.}}</ref><ref name="redondo_2021">{{cite journal |last1=Redondo |first1=Natalia |last2=Zaldívar-López |first2=Sara |last3=Garrido |first3=Juan J. |last4=Montoya |first4=Maria |title=SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns |journal=Frontiers in Immunology |date=7 July 2021 |volume=12 |article-number=708264 |doi=10.3389/fimmu.2021.708264|pmid=34305949 |pmc=8293742 |doi-access=free }}</ref>
|-
|[[ORF1ab]]<br />{{UniProt|P0C6X7}}
|Replicase/transcriptase polyprotein (pp1ab) <br />(''nonstructural proteins'')
|-
|ORF2<br />{{UniProt|P59594}}
|[[Coronavirus spike protein|Spike]] (S) protein, virus binding and entry <br />(''structural protein'')
|-
|[[ORF3a]]<br />{{UniProt|P59632}}||Interacts with S, E, M structural proteins; <br />[[Ion channel]] activity; <br />Upregulates [[cytokine]]s and [[chemokine]]s such as [[Interleukin 8|IL-8]] and [[CCL5|RANTES]]; <br />Upregulates [[NF-κB]] and [[C-Jun N-terminal kinases|JNK]]; <br />Induces [[apoptosis]] and [[Induced cell cycle arrest|cell cycle arrest]], via [[Caspase 8]] and [[Caspase-9|-9]], <br />and by [[Bcl-2-associated X protein|Bax]], [[p53]], and [[P38 mitogen-activated protein kinases|p38 MAP kinase]]
|-
|[[ORF3b]]<br />{{UniProt|P59633}} ||Upregulates [[cytokine]]s and [[chemokine]]s by [[RUNX1]]b; <br />Inhibits [[Interferon|Type I IFN]] production and signaling; <br />Induces apoptosis and [[Induced cell cycle arrest|cell cycle arrest]];
|-
|[[ORF3c]]<br />{{UniProt|P0DTG1}}||Unknown; first identified in SARS-CoV-2 but also present in SARS-CoV
|-
|[[ORF3d]]<br />{{UniProt|P0DTG0}}||Novel gene in SARS-CoV-2, of unknown function
|-
|ORF4<br />{{UniProt|P59637}}
|[[coronavirus envelope protein|Envelope]] (E) protein, virus assembly and budding <br />(''structural protein'')
|-
|ORF5<br />{{UniProt|P59596}}
|[[coronavirus membrane protein|Membrane]] (M) protein, virus assembly and budding <br />(''structural protein'')
|-
|[[ORF6]]<br />{{UniProt|P59634}} || Enhances cellular DNA synthesis; <br />Inhibits Type I IFN production and signaling
|-
|[[ORF7a]]<br />{{UniProt|P59635}}|| Inhibits cellular protein synthesis; <br />Induces inflammatory response by [[NF-κB|NF-kappaB]] and [[Interleukin 8|IL-8 promotor]]; <br />Upregulate chemokines such as IL-8 and RANTES; <br />Upregulates JNK, p38 MAP kinase; <br />Induces apoptosis and cell cycle arrest
|-
| [[ORF7b]]<br />{{UniProt|Q7TFA1}} || Unknown
|-
| [[ORF8a]]<br />{{Uniprot|Q7TFA0}} || Induces apoptosis through [[Mitochondrion|mitochondria]] pathway
|-
| [[ORF8b]]<br />{{UniProt|Q80H93}} || Enhances cellular DNA synthesis, also known as X5.
|-
|ORF9a<br />{{UniProt|P59595}}
|[[coronavirus nucleocapsid protein|Nucleocapsid]] (N) protein, viral RNA packaging <br />(''structural protein'')
|-
| [[ORF9b]]<br />{{UniProt|P59636}} || Induces apoptosis
|-
| [[ORF9c]]<br />{{UniProt|Q7TLC7}} || Also known as ORF14; function unknown and may not be protein-coding
|-
| [[ORF10]]<br />{{UniProt|A0A663DJA2}} || Novel gene in SARS-CoV-2, of unknown function; may not be protein-coding
|-
| colspan="2" style="text-align: center;" | ''[[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.<ref name=McBride2012>{{cite journal | vauthors = McBride R, Fielding BC | title = The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis | journal = Viruses | volume = 4 | issue = 11 | pages = 2902–23 | date = November 2012 | pmid = 23202509 | pmc = 3509677 | doi = 10.3390/v4112902 | doi-access = free }}</ref> ORFs 1a and 1b encode the replicase/transcriptase polyprotein, and later ORFs 2, 4, 5, and 9a encode, respectively, the four major structural proteins: [[coronavirus spike protein|spike]] (S), [[coronavirus envelope protein|envelope]] (E), [[coronavirus membrane protein|membrane]] (M), and [[coronavirus nucleocapsid protein|nucleocapsid]] (N).<ref>{{cite journal | vauthors = Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, Guan Y, Rozanov M, Spaan WJ, Gorbalenya AE | display-authors = 6 | title = Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage | journal = Journal of Molecular Biology | volume = 331 | issue = 5 | pages = 991–1004 | date = August 2003 | pmid = 12927536 | doi = 10.1016/S0022-2836(03)00865-9 | pmc = 7159028 | quote = See Figure 1. | doi-access = free }}</ref> The later ORFs also encode for eight unique proteins (orf3a to orf9b), known as the [[viral accessory protein|accessory proteins]], many with no known homologues. The different functions of the accessory proteins are not well understood.<ref name=McBride2012/>

SARS coronaviruses have been genetically engineered in several laboratories.<ref>{{cite journal |last1=Kaina |first1=Bernd |title=On the Origin of SARS-CoV-2: Did Cell Culture Experiments Lead to Increased Virulence of the Progenitor Virus for Humans? |journal=In Vivo |date=2021 |volume=35 |issue=3 |pages=1313–1326 |doi=10.21873/invivo.12384|pmid=33910809 |pmc=8193286 |doi-access=free }}</ref>

==Phylogenetics==
[[File:Phylogenetic analysis of SARS-CoV-2 and representative sarbecoviruses and geographical context.webp|thumb|upright=1.75|[[Phylogenetic tree]] of SARS-CoV-2 and closely related betacoronaviruses (left) and their geographic context (right)]]
[[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.<ref name="pmid32007145">{{cite journal| vauthors=Lu R, Zhao X, Li J, Niu P, Yang B, Wu H | display-authors=etal| title=Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. | journal=Lancet | year= 2020 | volume= 395 | issue= 10224 | pages= 565–574 | pmid=32007145 | doi=10.1016/S0140-6736(20)30251-8 | pmc=7159086 }}</ref><ref name="CVSG"/>
{{Clade|label1='''SARSr-CoV'''|1={{Clade|1={{Clade|1={{Clade|1=Bat CoV BtKY72}}
                                                |2={{Clade|1=Bat CoV BM48-31}}
                                         }}
                                      |2= {{Clade|1= {{Clade|1={{Clade|1={{Clade|1=SARS-CoV-1 related coronavirus}}}}}}
                                                 |2= {{Clade|1={{Clade|1={{Clade|1=SARS-CoV-2 related coronavirus}}}}}}
                                          }}
                                }}
}}

===SARS-CoV-1 related===
{{SARS-CoV-1 related coronavirus}}

===SARS-CoV-2 related===
{{SARS-CoV-2 related coronavirus}}

== Morphology ==
[[File:SARS-CoV-2 without background.png|thumb|right|Illustration created at the [[Centers for Disease Control and Prevention]] (CDC), reveals ultrastructural morphology exhibited by coronaviruses; note the [[coronavirus spike protein|spikes]] that adorn the outer surface, which impart the look of a corona surrounding the [[virion]].<ref>{{cite journal |author-last=Sonnevend |author-first=Julia |date=December 2020 |title=A virus as an icon: the 2020 pandemic in images |url=https://link.springer.com/content/pdf/10.1057/s41290-020-00118-7.pdf |editor1-last=Alexander |editor1-first=Jeffrey C. |editor2-last=Jacobs |editor2-first=Ronald N. |editor3-last=Smith |editor3-first=Philip |journal=American Journal of Cultural Sociology |location=[[Basingstoke]] |publisher=[[Palgrave Macmillan]] |volume=8 |issue=3: ''The COVID Crisis and Cultural Sociology: Alone Together'' |pages=451–461 |doi=10.1057/s41290-020-00118-7 |pmid=33042541 |pmc=7537773 |doi-access=free |issn=2049-7113 |eissn=2049-7121}}</ref>]]
[[File:Coronavirus virion structure.svg|thumb|right|Illustration of SARSr-CoV [[virion]]]]

The morphology of the SARS-related coronavirus is characteristic of the coronavirus family as a whole. The viruses are large [[Pleomorphism (cytology)|pleomorphic]] spherical particles with bulbous surface projections that form a corona around the particles in electron micrographs.<ref>{{cite journal | vauthors = Goldsmith CS, Tatti KM, Ksiazek TG, Rollin PE, Comer JA, Lee WW, Rota PA, Bankamp B, Bellini WJ, Zaki SR | display-authors = 6 | title = Ultrastructural characterization of SARS coronavirus | journal = Emerging Infectious Diseases | volume = 10 | issue = 2 | pages = 320–6 | date = February 2004 | pmid = 15030705 | pmc = 3322934 | doi = 10.3201/eid1002.030913 | quote = Virions acquired an envelope by budding into the cisternae and formed mostly spherical, sometimes pleomorphic, particles that averaged 78 nm in diameter (Figure 1A). }}</ref> The size of the virus particles is in the 80–90&nbsp;nm range. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells.<ref>{{cite journal | vauthors = Neuman BW, Adair BD, Yoshioka C, Quispe JD, Orca G, Kuhn P, Milligan RA, Yeager M, Buchmeier MJ | display-authors = 6 | title = Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy | journal = Journal of Virology | volume = 80 | issue = 16 | pages = 7918–28 | date = August 2006 | pmid = 16873249 | pmc = 1563832 | doi = 10.1128/JVI.00645-06 | quote = Particle diameters ranged from 50 to 150 nm, excluding the spikes, with mean particle diameters of 82 to 94 nm; Also See Figure 1 for double shell. }}</ref>

The [[viral envelope]] consists of a [[lipid bilayer]] where the [[coronavirus membrane protein|membrane]] (M), [[coronavirus envelope protein|envelope]] (E) and [[Coronavirus spike protein|spike]] (S) proteins are anchored.<ref name="Lai_1997">{{cite journal | vauthors = Lai MM, Cavanagh D | title = The molecular biology of coronaviruses | journal = Advances in Virus Research | volume = 48 | pages = 1–100 | date = 1997 | pmid = 9233431 | doi = 10.1016/S0065-3527(08)60286-9 | pmc = 7130985 | isbn = 9780120398485 | doi-access = free }}</ref> The spike proteins provide the virus with its bulbous surface projections, known as [[peplomer]]s. The spike protein's interaction with its complement [[Viral entry|host cell receptor]] is central in determining the [[tissue tropism]], [[infectivity]], and [[Host tropism|species range]] of the virus.<ref>{{cite book | vauthors = Masters PS | title = The molecular biology of coronaviruses | volume = 66 | pages = 193–292 | date = 1 January 2006 | pmid = 16877062 | doi = 10.1016/S0065-3527(06)66005-3 | publisher = Academic Press | isbn = 9780120398690 | quote = Nevertheless, the interaction between S protein and receptor remains the principal, if not sole, determinant of coronavirus host species range and tissue tropism. | series = Advances in Virus Research | pmc = 7112330 }}</ref><ref>{{cite journal | vauthors = Cui J, Li F, Shi ZL | title = Origin and evolution of pathogenic coronaviruses | journal = Nature Reviews. Microbiology | volume = 17 | issue = 3 | pages = 181–192 | date = March 2019 | pmid = 30531947 | doi = 10.1038/s41579-018-0118-9 | pmc = 7097006 | quote = Different SARS-CoV strains isolated from several hosts vary in their binding affinities for human ACE2 and consequently in their infectivity of human cells76,78 (Fig. 6b) }}</ref>

Inside  the envelope, there is the [[Capsid|nucleocapsid]], which is formed from multiple copies of the [[coronavirus nucleocapsid protein|nucleocapsid]] (N) protein, which are bound to the positive-sense single-stranded (~30 [[Base pair|kb]]) RNA genome in a continuous [[Bead|beads-on-a-string]] type conformation.<ref>{{cite book | vauthors = Fehr AR, Perlman S | title = Coronaviruses | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | series = Methods in Molecular Biology | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc | quote = See section: Virion Structure. }}</ref><ref>{{cite journal | vauthors = Chang CK, Hou MH, Chang CF, Hsiao CD, Huang TH | title = The SARS coronavirus nucleocapsid protein--forms and functions | journal = Antiviral Research | volume = 103 | pages = 39–50 | date = March 2014 | pmid = 24418573 | doi = 10.1016/j.antiviral.2013.12.009 | pmc = 7113676 | quote = See Figure 4c. | doi-access = free }}</ref> The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus  when it is outside the host.<ref>{{cite journal | vauthors = Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, Droese B, Klaus JP, Makino S, Sawicki SG, Siddell SG, Stamou DG, Wilson IA, Kuhn P, Buchmeier MJ | display-authors = 6 | title = A structural analysis of M protein in coronavirus assembly and morphology | journal = Journal of Structural Biology | volume = 174 | issue = 1 | pages = 11–22 | date = April 2011 | pmid = 21130884 | pmc = 4486061 | doi = 10.1016/j.jsb.2010.11.021 | quote = See Figure 10. }}</ref>

== Life cycle ==
SARS-related coronavirus follows the replication strategy typical of all coronaviruses.<ref name = "Fehr_2015" /><ref>{{cite book |title=Molecular Biology of the SARS-Coronavirus |doi=10.1007/978-3-642-03683-5|isbn=978-3-642-03682-8|year=2010|editor1-last=Lal|editor1-first=Sunil K | name-list-style = vanc }}</ref>

=== Attachment and entry ===
[[File:Coronavirus replication cycle.jpg|thumb|[[Coronavirus]] [[viral replication|replication]] cycle]]

The attachment of the SARS-related coronavirus to the host cell is mediated by the spike protein and its receptor.<ref name=":2">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc | quote = See section: Coronavirus Life Cycle – Attachment and Entry }}</ref> The spike protein receptor binding domain (RBD) recognizes and attaches to the [[angiotensin-converting enzyme 2]] (ACE2) receptor.<ref name="pmid24172901"/> Following attachment, the virus can enter the host cell by two different paths. The path the virus takes depends on the host [[protease]] available to cleave and activate the receptor-attached spike protein.<ref name=":6">{{cite journal | vauthors = Simmons G, Zmora P, Gierer S, Heurich A, Pöhlmann S | title = Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research | journal = Antiviral Research | volume = 100 | issue = 3 | pages = 605–14 | date = December 2013 | pmid = 24121034 | pmc = 3889862 | doi = 10.1016/j.antiviral.2013.09.028 | quote = See Figure 2. }}</ref> A notably difference between SARS-CoV-1 and SARS-CoV-2, is that SARS-CoV-2 is pre-cleaved due to its furin cleavage site.<ref>{{Cite journal |last1=Jaimes |first1=Javier A. |last2=Millet |first2=Jean K. |last3=Whittaker |first3=Gary R. |date=2020-06-26 |title=Proteolytic Cleavage of the SARS-CoV-2 Spike Protein and the Role of the Novel S1/S2 Site |journal=iScience |volume=23 |issue=6 |article-number=101212 |doi=10.1016/j.isci.2020.101212 |issn=2589-0042 |pmc=7255728 |pmid=32512386 |bibcode=2020iSci...23j1212J }}</ref>

The attachment of sarbecoviruses to ACE2 has been shown to be an [[evolutionarily conserved]] feature, present in many (but not all) species of the taxon with ACE2 using representatives in Africa, Asia, and Europe.<ref>{{Cite journal |last1=Starr |first1=Tyler N. |last2=Zepeda |first2=Samantha K. |last3=Walls |first3=Alexandra C. |last4=Greaney |first4=Allison J. |last5=Alkhovsky |first5=Sergey |last6=Veesler |first6=David |last7=Bloom |first7=Jesse D. |date=2022-03-01 |title=ACE2 binding is an ancestral and evolvable trait of sarbecoviruses |journal=Nature |language=en |volume=603 |issue=7903 |pages=913–918 |doi=10.1038/s41586-022-04464-z |pmid=35114688 |pmc=8967715 |bibcode=2022Natur.603..913S |issn=1476-4687}}</ref>

The first path the SARS coronavirus can take to enter the host cell is by [[endocytosis]] and uptake of the virus in an [[endosome]]. The receptor-attached spike protein is then activated by the host's pH-dependent [[cysteine protease]] [[Cathepsin L1|cathepsin L]]. Activation of the receptor-attached spike protein causes a [[conformational change]], and the subsequent fusion of the viral envelope with the [[Lipid bilayer|endosomal wall]].<ref name=":6" />

Alternatively, the virus can enter the host cell directly by [[Proteolysis|proteolytic]] cleavage of the receptor-attached spike protein by the host's [[TMPRSS2]] or [[TMPRSS11D]] [[serine protease]]s at the cell surface.<ref>{{cite journal | vauthors = Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pöhlmann S | title = TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein | journal = Journal of Virology | volume = 88 | issue = 2 | pages = 1293–307 | date = January 2014 | pmid = 24227843 | pmc = 3911672 | doi = 10.1128/JVI.02202-13 | quote = The SARS-CoV can hijack two cellular proteolytic systems to ensure the adequate processing of its S protein. Cleavage of SARS-S can be facilitated by cathepsin L, a pH-dependent endo-/lysosomal host cell protease, upon uptake of virions into target cell endosomes (25). Alternatively, the type II transmembrane serine proteases (TTSPs) TMPRSS2 and HAT can activate SARS-S, presumably by cleavage of SARS-S at or close to the cell surface, and activation of SARS-S by TMPRSS2 allows for cathepsin L-independent cellular entry (26,–28). }}</ref><ref>{{cite journal | vauthors = Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY | title = Coronaviruses - drug discovery and therapeutic options | journal = Nature Reviews. Drug Discovery | volume = 15 | issue = 5 | pages = 327–47 | date = May 2016 | pmid = 26868298 | doi = 10.1038/nrd.2015.37 | pmc = 7097181 | quote = S is activated and cleaved into the S1 and S2 subunits by other host proteases, such as transmembrane protease serine 2 (TMPRSS2) and TMPRSS11D, which enables cell surface non-endosomal virus entry at the plasma membrane. }}</ref> In the SARS coronavirus, the activation of the [[C-terminus|C-terminal part]] of the spike protein triggers the fusion of the viral envelope with the host cell membrane by inducing conformational changes which are not fully understood.<ref name="pmid316509562">{{cite journal | vauthors = Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, Benlekbir S, Rubinstein JL, Rini JM | display-authors = 6 | title = The human coronavirus HCoV-229E S-protein structure and receptor binding | journal = eLife | volume = 8 | date = October 2019 | article-number = e51230 | pmid = 31650956 | pmc = 6970540 | doi = 10.7554/eLife.51230 | doi-access = free }}</ref>

=== Genome translation ===
{| class="wikitable mw-collapsible mw-collapsed" |col2style=text-align:right style="width:auto; float:right; clear:right; margin:0px 0px 0.5em 1em"
!colspan=2| Function of coronavirus <br /> nonstructural proteins (nsps)<ref name=":1">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc | quote = See Table 2. }}</ref>
|-
! Protein || Function
|-
| nsp1 || Promotes host [[Messenger RNA|mRNA]] degradation, blocks host [[Translation (biology)|translation]];<ref>{{cite journal |last1=Rao |first1=S |last2=Hoskins |first2=I |last3=Tonn |first3=T |last4=Garcia |first4=PD |last5=Ozadam |first5=H |last6=Sarinay Cenik |first6=E |last7=Cenik |first7=C |title=Genes with 5' terminal oligopyrimidine tracts preferentially escape global suppression of translation by the SARS-CoV-2 Nsp1 protein. |journal=RNA |date=September 2021 |volume=27 |issue=9 |pages=1025–1045 |doi=10.1261/rna.078661.120 |pmid=34127534|pmc=8370740 }}</ref> <br />blocks [[Innate immune system|innate immune response]]
|-
| nsp2 || Binds to [[prohibitin]] proteins; <br />unknown function
|-
| nsp3 ||[[Protein domain|Multidoman]] [[transmembrane protein]]; interacts with [[Capsid|N protein]]; promotes [[cytokine]] expression; [[Papain|PLPro]] domain cleaves [[Proteolysis|polyprotein]] pp1ab and blocks host's innate immune response; other domains unknown functions
|-
| nsp4 || Transmembrane [[scaffold protein]]; <br />allows proper structure for [[Lipid bilayer|double membrane vesicles]] (DMVs)
|-
| nsp5 ||[[C30 Endopeptidase|3CLPro]] cleaves polyprotein pp1ab
|-
| nsp6 || Transmembrane scaffold protein; <br />unknown function
|-
| nsp7 || Forms [[Oligomer|hexadecameric]] complex with nsp8; [[Processivity|processivity clamp]] for [[RNA-dependent RNA polymerase|RdRp]] (nsp12)
|-
| nsp8 || Forms hexadecameric complex with nsp7; processivity clamp for RdRp (nsp12); acts as a [[primase]]
|-
| nsp9 ||[[RNA-binding protein]] (RBP)
|-
| nsp10 || nsp16 and nsp14 [[Cofactor (biochemistry)|cofactor]]; forms heterodimer with both; stimulates [[2'-O-methylation|2-O-MT]] (nsp16) and [[Exoribonuclease|ExoN]] (nsp14) activity
|-
| nsp11 || Unknown function
|-
| nsp12 ||[[RNA-dependent RNA polymerase]] (RdRp)
|-
| nsp13 ||[[Helicase|RNA helicase]], [[triphosphatase|5′ triphosphatase]]
|-
| nsp14 ||[[Methyltransferase|N7 Methyltransferase]], [[exoribonuclease|3′-5′ exoribonuclease]] (ExoN); N7 MTase adds [[five-prime cap|5′ cap]], ExoN [[proofreading (biology)|proofreads genome]]
|-
| nsp15 ||[[Endoribonuclease]] (NendoU)
|-
| nsp16 ||[[2'-O-methylation|2′-O-Methyltransferase]] (2-O-MT); protects viral RNA from [[MDA5]]
|-
|}
After fusion the nucleocapsid passes into the [[cytoplasm]], where the viral genome is released.<ref name=":2" /> The genome [[ribosome-binding site|acts as a messenger RNA]], and the cell's ribosome [[translation (biology)|translates]] two-thirds of the genome, which corresponds to the open reading frame [[ORF1a]] and [[ORF1b]], into two large overlapping polyproteins, pp1a and pp1ab.

The larger polyprotein pp1ab is a result of a [[ribosomal frameshift|-1 ribosomal frameshift]] caused by a [[slippery sequence]] (UUUAAAC) and a downstream [[Nucleic acid secondary structure|RNA pseudoknot]] at the end of open reading frame ORF1a.<ref>{{cite journal | vauthors = Masters PS | title = The molecular biology of coronaviruses | journal = Advances in Virus Research | volume = 66 | pages = 193–292 | date = 1 January 2006 | pmid = 16877062 | doi = 10.1016/S0065-3527(06)66005-3 | publisher = Academic Press | pmc = 7112330 | isbn = 9780120398690 | quote =See Figure 8. | doi-access = free }}</ref> The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b.<ref name=":3" />

The polyproteins contain their own [[C30 Endopeptidase|proteases]],  [[Papain|PLpro]] and [[C30 Endopeptidase|3CLpro]], which cleave the polyproteins at different specific sites. The cleavage of polyprotein pp1ab yields 16 nonstructural proteins (nsp1 to nsp16). Product proteins include various replication  proteins such as [[RNA-dependent RNA polymerase]] (RdRp), [[RNA helicase]], and [[exoribonuclease]] (ExoN).<ref name=":3">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc |quote=See section: Replicase Protein Expression }}</ref>

The two SARS-CoV-2 proteases (PLpro and 3CLpro) also interfere with the immune system response to the viral infection by cleaving three immune system proteins. PLpro cleaves [[IRF3]] and 3CLpro cleaves both [[NLRP12]] and [[TAB1]]. "Direct cleavage of IRF3 by NSP3 could explain the blunted Type-I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients."<ref>{{cite journal |url=https://www.biorxiv.org/content/10.1101/2020.06.05.135699v1 |title=SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts |author=Mehdi Moustaqil |s2cid=219604020 |journal=bioRxiv|date=5 June 2020|article-number=2020.06.05.135699 |doi=10.1101/2020.06.05.135699 |doi-access=free }}</ref>

=== Replication and transcription ===
[[File:Replication-transcription complex for Coronaviruses.tif|thumb|Model of the [[replicase]]-transcriptase complex of a [[coronavirus]]. [[RNA-dependent RNA polymerase|RdRp]] for [[DNA replication|replication]] (red), [[Exoribonuclease|ExoN]] for [[proofreading (biology)|proofreading]] (dark blue), ExoN cofactor (yellow), [[RNA-binding protein|RBPs]] to avoid [[nucleic acid secondary structure|secondary structure]] (light blue), [[DNA clamp|RNA sliding clamp]] for [[processivity]] and [[primase]] [[protein domain|domain]] for [[primer (molecular biology)|priming]] (green/orange), and a [[helicase]] to unwind RNA (downstream).]]

A number of the nonstructural replication proteins coalesce to form a [[protein complex|multi-protein]] replicase-transcriptase complex (RTC).<ref name=":3" /> The main replicase-transcriptase protein is the [[RNA-dependent RNA polymerase]] (RdRp). It is directly involved in the [[DNA replication|replication]] and [[transcription (biology)|transcription]] of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process.<ref name=":1" />

The protein nsp14 is a [[Exoribonuclease|3'-5' exoribonuclease]] which provides extra fidelity to the replication process. The exoribonuclease provides a [[proofreading (biology)|proofreading]] function to the complex which the RNA-dependent RNA polymerase lacks. Similarly, proteins nsp7 and nsp8 form a hexadecameric sliding clamp as part of the complex which greatly increases the [[processivity]] of the RNA-dependent RNA polymerase.<ref name=":1" /> The coronaviruses require the increased fidelity and processivity during RNA synthesis because of the relatively large genome size in comparison to other RNA viruses.<ref name="SextonSmith2016">{{cite journal|vauthors=Sexton NR, Smith EC, Blanc H, Vignuzzi M, Peersen OB, Denison MR|date=August 2016|title=Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens|journal=Journal of Virology|volume=90|issue=16|pages=7415–28|doi=10.1128/JVI.00080-16|pmc=4984655|pmid=27279608|quote=Finally, these results, combined with those from previous work (33, 44), suggest that CoVs encode at least three proteins involved in fidelity (nsp12-RdRp, nsp14-ExoN, and nsp10), supporting the assembly of a multiprotein replicase-fidelity complex, as described previously (38).}}</ref>

One of the main functions of the replicase-transcriptase complex is to transcribe the viral genome. RdRp directly mediates the [[transcription (biology)|synthesis]] of  negative-sense [[subgenomic RNA]] molecules from the positive-sense genomic RNA. This is followed by the transcription of these negative-sense subgenomic RNA molecules to their corresponding positive-sense [[Messenger RNA|mRNAs]].<ref name=":5">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc |quote=See section: Corona Life Cycle – Replication and Transcription}}</ref>

The other important function of the replicase-transcriptase complex is to replicate the viral genome. RdRp directly mediates the [[DNA replication|synthesis]] of negative-sense genomic RNA from the positive-sense genomic RNA. This is followed by the replication of positive-sense genomic RNA from the negative-sense genomic RNA.<ref name=":5" /> SARS-CoV replication and transcription mainly occurs in virus-induced double-membrane vesicles (DMVs) made from altered host [[endoplasmic reticulum]].<ref name="Andronov2024">{{Cite journal |vauthors=Andronov L, Han M, Zhu Y, Balaji A, Roy AR, Barentine AE, Patel P, Garhyan J, Qi LS, Moerner WE |date=May 2024 |title=Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles |journal=Nature Communications |volume=15 |issue=1 |article-number=4644 |bibcode=2024NatCo..15.4644A |doi=10.1038/s41467-024-48991-x |pmc=11143195 |pmid=38821943}}</ref>

The replicated positive-sense genomic RNA becomes the genome of the [[viral shedding|progeny viruses]]. The various smaller mRNAs are transcripts from the last third of the virus genome which follows the reading frames ORF1a and ORF1b. These mRNAs are translated into the four structural proteins (S, E, M, and N) that will become part of the progeny virus particles and also eight other accessory proteins (orf3 to orf9b) which assist the virus.<ref>{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc | quote = See Figure 1. }}</ref>

===Recombination===
When two SARS-CoV [[genome]]s are present in a host cell, they may interact with each other to form recombinant genomes that can be transmitted to progeny viruses.  Recombination likely occurs during genome replication when the [[RNA-dependent RNA polymerase|RNA polymerase]] switches from one template to another (copy choice recombination).<ref name = Zhang2005/>  Human SARS-CoV appears to have had a complex history of [[genetic recombination|recombination]] between ancestral [[coronavirus]]es that were hosted in several different animal groups.<ref name="Zhang2005">Zhang XW, Yap YL, Danchin A.  Testing the hypothesis of a recombinant origin of the SARS-associated coronavirus.  Arch Virol. 2005 Jan;150(1):1-20. Epub 2004 Oct 11.  PMID 15480857</ref><ref>Stanhope MJ, Brown JR, Amrine-Madsen H.  Evidence from the evolutionary analysis of nucleotide sequences for a recombinant history of SARS-CoV.  Infect Genet Evol. 2004 Mar;4(1):15-9. PMID 15019585</ref>

=== Assembly and release ===
[[Translation (biology)|RNA translation]] occurs  inside the [[endoplasmic reticulum]]. The viral structural proteins S,  E and M  move along the secretory pathway into the [[vesicular-tubular cluster|Golgi intermediate compartment]]. There, the M proteins direct most protein-protein interactions required for assembly of viruses following its binding to the nucleocapsid.<ref name=":4">{{cite book | vauthors = Fehr AR, Perlman S | chapter = Coronaviruses: An Overview of Their Replication and Pathogenesis | title = Coronaviruses | volume = 1282 | pages = 1–23 | date = 2015 | pmid = 25720466 | pmc = 4369385 | doi = 10.1007/978-1-4939-2438-7_1 | publisher = Springer | isbn = 978-1-4939-2438-7 | series = Methods in Molecular Biology | editor-first = Helena Jane | editor-last = Maier | editor2-first = Erica | editor2-last = Bickerton | editor3-first = Paul | editor3-last = Britton | name-list-style = vanc |quote=See section: Coronavirus Life Cycle – Assembly and Release }}</ref> Progeny viruses are released from the host cell by [[exocytosis]] through secretory vesicles.<ref name=":4" />

== See also ==
{{Portal|COVID-19|Viruses}}
* [[Bat SARS-like coronavirus WIV1]] (SL-CoV-WIV1)
* [[SHC014-CoV|Bat SARS-like coronavirus RsSHC014]]
* [[RaTG13|Bat coronavirus RaTG13]]
* [[Civet SARS-CoV]]

== Notes ==
{{Reflist|group=note}}

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin|2}}
* {{cite journal | vauthors = Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, Nicholls J, Yee WK, Yan WW, Cheung MT, Cheng VC, Chan KH, Tsang DN, Yung RW, Ng TK, Yuen KY | display-authors = 6 | title = Coronavirus as a possible cause of severe acute respiratory syndrome | journal = Lancet | volume = 361 | issue = 9366 | pages = 1319–25 | date = April 2003 | pmid = 12711465 | doi = 10.1016/s0140-6736(03)13077-2 | pmc = 7112372 | doi-access = free }}
* {{cite journal | vauthors = Rota PA, Oberste MS, Monroe SS, Nix WA, Campagnoli R, Icenogle JP, Peñaranda S, Bankamp B, Maher K, Chen MH, Tong S, Tamin A, Lowe L, Frace M, DeRisi JL, Chen Q, Wang D, Erdman DD, Peret TC, Burns C, Ksiazek TG, Rollin PE, Sanchez A, Liffick S, Holloway B, Limor J, McCaustland K, Olsen-Rasmussen M, Fouchier R, Günther S, Osterhaus AD, Drosten C, Pallansch MA, Anderson LJ, Bellini WJ | display-authors = 6 | title = Characterization of a novel coronavirus associated with severe acute respiratory syndrome | journal = Science | volume = 300 | issue = 5624 | pages = 1394–9 | date = May 2003 | pmid = 12730500 | doi = 10.1126/science.1085952 | bibcode = 2003Sci...300.1394R | doi-access = free | hdl = 1765/3917 | hdl-access = free }}
* {{cite journal | vauthors = Marra MA, Jones SJ, Astell CR, Holt RA, Brooks-Wilson A, Butterfield YS, Khattra J, Asano JK, Barber SA, Chan SY, Cloutier A, Coughlin SM, Freeman D, Girn N, Griffith OL, Leach SR, Mayo M, McDonald H, Montgomery SB, Pandoh PK, Petrescu AS, Robertson AG, Schein JE, Siddiqui A, Smailus DE, Stott JM, Yang GS, Plummer F, Andonov A, Artsob H, Bastien N, Bernard K, Booth TF, Bowness D, Czub M, Drebot M, Fernando L, Flick R, Garbutt M, Gray M, Grolla A, Jones S, Feldmann H, Meyers A, Kabani A, Li Y, Normand S, Stroher U, Tipples GA, Tyler S, Vogrig R, Ward D, Watson B, Brunham RC, Krajden M, Petric M, Skowronski DM, Upton C, Roper RL | display-authors = 6 | title = The Genome sequence of the SARS-associated coronavirus | journal = Science | volume = 300 | issue = 5624 | pages = 1399–404 | date = May 2003 | pmid = 12730501 | doi = 10.1126/science.1085953 | bibcode = 2003Sci...300.1399M | doi-access = free }}
* {{cite journal | vauthors = Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, Guan Y, Rozanov M, Spaan WJ, Gorbalenya AE | s2cid = 14974326 | display-authors = 6 | title = Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage | journal = Journal of Molecular Biology | volume = 331 | issue = 5 | pages = 991–1004 | date = August 2003 | pmid = 12927536 | doi = 10.1016/S0022-2836(03)00865-9 | pmc = 7159028 | citeseerx = 10.1.1.319.7007 }}
* {{cite journal | vauthors = Yount B, Roberts RS, Lindesmith L, Baric RS | title = Rewiring the severe acute respiratory syndrome coronavirus (SARS-CoV) transcription circuit: engineering a recombination-resistant genome | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 33 | pages = 12546–51 | date = August 2006 | pmid = 16891412 | pmc = 1531645 | doi = 10.1073/pnas.0605438103 | bibcode = 2006PNAS..10312546Y | doi-access = free }}
* {{cite book | veditors = Thiel V | title = Coronaviruses: Molecular and Cellular Biology | edition = 1st | publisher = Caister Academic Press | year = 2007 |  isbn =  978-1-904455-16-5 }}
* {{cite book | vauthors = Enjuanes L, Sola I, Zúñiga S, Almazán F |year=2008 |chapter=Coronavirus Replication and Interaction with Host |title=Animal Viruses: Molecular Biology |publisher=Caister Academic Press |isbn= 978-1-904455-22-6 | veditors = Mettenleiter TC, Sobrino F}}
{{Refend}}

== External links ==
* {{Commons category-inline}}
* {{Wikispecies-inline}}
* [https://web.archive.org/web/20030423172854/http://www.who.int/mediacentre/releases/2003/pr31/en/ WHO press release identifying and naming the SARS virus] (archived 23 April 2003)
* [http://www.bcgsc.ca/bioinfo/SARS/ The SARS virus genetic map] {{Webarchive|url=https://web.archive.org/web/20060818170451/http://www.bcgsc.ca/bioinfo/SARS |date=18 August 2006 }}
* [https://www.science.org/action/doSearch?AllField=SARS ''Science'' special on the SARS virus] (free content: no registration required)
* {{webarchive |url=https://web.archive.org/web/20050301194019/http://www.health.library.mcgill.ca/resource/sars.htm |date=1 March 2005 |title=McGill University SARS Resources }}
* [https://web.archive.org/web/20160412085632/http://www.cdc.gov/ncidod/sars/ U.S. Centers for Disease Control and Prevention (CDC) SARS home] (archived 12 April 2016)

{{Coronaviridae}}
{{SARS}}
{{Viral diseases}}
{{Zoonotic viral diseases}}
{{Taxonbar|from=Q278567}}
{{Authority control}}

[[Category:SARS-related coronavirus| ]]