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Severe acute respiratory syndrome–related coronavirus

This article is about a species of coronavirus comprising multiple strains. For the strain that causes SARS, see Severe acute respiratory syndrome coronavirus 1. For the strain that causes COVID-19, see Severe acute respiratory syndrome coronavirus 2.

Severe acute respiratory syndrome–related coronavirus (SARSr-CoV or SARS-CoV) is a species of virus consisting of many known strains phylogenetically related to severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) that have been shown to possess the capability to infect humans, bats, and certain other mammals. These enveloped, positive-sense single-stranded RNA viruses enter host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. The SARSr-CoV species is a member of the genus Betacoronavirus and of the subgenus Sarbecovirus.

Severe acute respiratory syndrome–related coronavirus
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
Strains
Synonyms
  • SARS coronavirus
  • SARS-related coronavirus
  • Severe acute respiratory syndrome coronavirus

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. There are hundreds of other strains of SARSr-CoV, which are only known to infect non-human species: bats are a major reservoir of many strains of SARSr-CoV; several strains have been identified in palm civets, which were likely ancestors of SARS-CoV-1.

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 in 2020 with the COVID-19 pandemic.

Contents

SARS-related coronavirus is a member of the genus Betacoronavirus (group 2) and monotypic of the subgenus Sarbecovirus (subgroup B). Sarbecoviruses, unlike embecoviruses or alphacoronaviruses, have only one papain-like proteinase (PLpro) instead of two in the open reading frame ORF1. 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.

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. 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 and SARS-CoV-2. 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.

Genome organization and viral proteins of SARS-CoV

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. The genome has the usual 5′ methylated cap and a 3′ polyadenylated tail. There are 265 nucleotides in the 5'UTR and 342 nucleotides in the 3'UTR.

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. 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.

Function of SARS-CoV
genome proteins (orf1a to orf9b)
Protein Function
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;
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
orf10
Q7TLC7
SARS-specific "protein 14"

The functions of several of the viral proteins are known. 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). 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.

SARS coronaviruses have been genetically engineered in several laboratories.

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.

SARSr‑CoV

Bat CoV BtKY72

Bat CoV BM48-31

SARS-CoV-1 related coronavirus

SARS-CoV-2 related coronavirus

SARS-CoV-1 related

A phylogenetic tree based on whole-genome sequences of SARS-CoV-1 and related coronaviruses is:

SARS‑CoV‑1 related coronavirus

16BO133 [zh], 82.8% to SARS-CoV-1, Rhinolophus ferrumequinum, North Jeolla, South Korea

Bat SARS CoV Rf1, 87.8% to SARS-CoV-1, Rhinolophus ferrumequinum, Yichang, Hubei

BtCoV HKU3, 87.9% to SARS-CoV-1, Rhinolophus sinicus, Hong kong and Guangdong

LYRa11 [zh], 90.9% to SARS-CoV-1, Rhinolophus affinis, Baoshan, Yunnan

Bat SARS-CoV/Rp3, 92.6% to SARS-CoV-1, Rhinolophus pearsoni, Nanning, Guangxi

Bat SL-CoV YNLF_31C, 93.5% to SARS-CoV-1, Rhinolophus ferrumequinum, Lufeng, Yunnan

Bat SL-CoV YNLF_34C, 93.5% to SARS-CoV-1, Rhinolophus ferrumequinum, Lufeng, Yunnan

SHC014-CoV, 95.4% to SARS-CoV-1, Rhinolophus sinicus, Kunming, Yunnan

WIV1, 95.6% to SARS-CoV-1, Rhinolophus sinicus, Kunming, Yunnan

WIV16, 96.0% to SARS-CoV-1, Rhinolophus sinicus Kunming, Yunnan

Civet SARS-CoV, 99.8% to SARS-CoV-1, Paguma larvata, market in Guangdong, China

SARS-CoV-1

SARS-CoV-2, 79% to SARS-CoV-1

SARS-CoV-2 related

A phylogenetic tree based on whole-genome sequences of SARS-CoV-2 and related coronaviruses is:

SARS‑CoV‑2 related coronavirus

(Bat) Rc-o319, 81% to SARS-CoV-2, Rhinolophus cornutus, Iwate, Japan

Bat SL-ZXC21, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang

Bat SL-ZC45, 88% to SARS-CoV-2, Rhinolophus pusillus, Zhoushan, Zhejiang

Pangolin SARSr-CoV-GX, 89% to SARS-CoV-2, Manis javanica, Smuggled from Southeast Asia

Pangolin SARSr-CoV-GD, 91% to SARS-CoV-2, Manis javanica, Smuggled from Southeast Asia

SARS-CoV-1, 79% to SARS-CoV-2


Illustration created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses; note the spikes that adorn the outer surface, which impart the look of a corona surrounding the virion.
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 pleomorphic spherical particles with bulbous surface projections that form a corona around the particles in electron micrographs. The size of the virus particles is in the 80–90 nm range. The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells.

The viral envelope consists of a lipid bilayer where the membrane (M), envelope (E) and spike (S) proteins are anchored. The spike proteins provide the virus with its bulbous surface projections. The spike protein's interaction with its complement host cell receptor is central in determining the tissue tropism, infectivity, and species range of the virus.

Inside the envelope, there is the nucleocapsid, which is formed from multiple copies of the nucleocapsid (N) protein, which are bound to the positive-sense single-stranded (~30 kb) RNA genome in a continuous beads-on-a-string type conformation. The lipid bilayer envelope, membrane proteins, and nucleocapsid protect the virus when it is outside the host.

SARS-related coronavirus follows the replication strategy typical of all coronaviruses.

Attachment and entry

The attachment of the SARS-related coronavirus to the host cell is mediated by the spike protein and its receptor. The spike protein receptor binding domain (RBD) recognizes and attaches to the angiotensin-converting enzyme 2 (ACE2) receptor. 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.

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 L. Activation of the receptor-attached spike protein causes a conformational change, and the subsequent fusion of the viral envelope with the endosomal wall.

Alternatively, the virus can enter the host cell directly by proteolytic cleavage of the receptor-attached spike protein by the host's TMPRSS2 or TMPRSS11D serine proteases at the cell surface. In the SARS coronavirus, the activation of the 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.

Genome translation

Function of coronavirus
nonstructural proteins (nsps)
Protein Function
nsp1 Promotes host mRNA degradation, blocks host translation;
blocks innate immune response
nsp2 Binds to prohibitin proteins;
unknown function
nsp3 Multidoman transmembrane protein; interacts with N protein; promotes cytokine expression; PLPro domain cleaves polyprotein pp1ab and blocks host's innate immune response; other domains unknown functions
nsp4 Transmembrane scaffold protein;
allows proper structure for double membrane vesicles (DMVs)
nsp5 3CLPro cleaves polyprotein pp1ab
nsp6 Transmembrane scaffold protein;
unknown function
nsp7 Forms hexadecameric complex with nsp8; processivity clamp for 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; forms heterodimer with both; stimulates 2-O-MT (nsp16) and ExoN (nsp14) activity
nsp11 Unknown function
nsp12 RNA-dependent RNA polymerase (RdRp)
nsp13 RNA helicase, 5′ triphosphatase
nsp14 N7 Methyltransferase, 3′-5′ exoribonuclease (ExoN); N7 MTase adds 5′ cap, ExoN proofreads genome
nsp15 Endoribonuclease (NendoU)
nsp16 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. The genome acts as a messenger RNA, and the cell's ribosome 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 -1 ribosomal frameshift caused by a slippery sequence (UUUAAAC) and a downstream RNA pseudoknot at the end of open reading frame ORF1a. The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b.

The polyproteins contain their own proteases, PLpro and 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).

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."

Replication and transcription

Model of the replicase-transcriptase complex of a coronavirus. RdRp for replication (red), ExoN for proofreading (dark blue), ExoN cofactor (yellow), RBPs to avoid secondary structure (light blue), RNA sliding clamp for processivity and primase domain for priming (green/orange), and a helicase to unwind RNA (downstream).

A number of the nonstructural replication proteins coalesce to form a multi-protein replicase-transcriptase complex (RTC). The main replicase-transcriptase protein is the RNA-dependent RNA polymerase (RdRp). It is directly involved in the replication and transcription of RNA from an RNA strand. The other nonstructural proteins in the complex assist in the replication and transcription process.

The protein nsp14 is a 3'-5' exoribonuclease which provides extra fidelity to the replication process. The exoribonuclease provides a 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. The coronaviruses require the increased fidelity and processivity during RNA synthesis because of the relatively large genome size in comparison to other RNA viruses.

One of the main functions of the replicase-transcriptase complex is to transcribe the viral genome. RdRp directly mediates the 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 mRNAs.

The other important function of the replicase-transcriptase complex is to replicate the viral genome. RdRp directly mediates the 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.

The replicated positive-sense genomic RNA becomes the genome of the 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.

Recombination

When two SARS-CoV genomes 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 polymerase switches from one template to another (copy choice recombination). Human SARS-CoV appears to have had a complex history of recombination between ancestral coronaviruses that were hosted in several different animal groups.

Assembly and release

RNA translation occurs inside the endoplasmic reticulum. The viral structural proteins S, E and M move along the secretory pathway into the Golgi intermediate compartment. There, the M proteins direct most protein-protein interactions required for assembly of viruses following its binding to the nucleocapsid.

Progeny viruses are released from the host cell by exocytosis through secretory vesicles.

  1. 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.
  1. "ICTV Taxonomy history: Severe acute respiratory syndrome-related coronavirus". International Committee on Taxonomy of Viruses (ICTV). Retrieved27 January 2019.
  2. Branswell H (9 November 2015). "SARS-like virus in bats shows potential to infect humans, study finds". Stat News. Retrieved20 February 2020.
  3. Wong AC, Li X, Lau SK, Woo PC (February 2019). "Global Epidemiology of Bat Coronaviruses". Viruses. 11 (2): 174. doi:10.3390/v11020174. PMC6409556. PMID 30791586. 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].
  4. Ge XY, Li JL, Yang XL, Chmura AA, Zhu G, Epstein JH, et al. (November 2013). "Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor". Nature. 503 (7477): 535–8. Bibcode:2013Natur.503..535G. doi:10.1038/nature12711. PMC5389864. PMID 24172901.
  5. "Virus Taxonomy: 2018 Release". International Committee on Taxonomy of Viruses (ICTV). October 2018. Retrieved13 January 2019.
  6. Woo PC, Huang Y, Lau SK, Yuen KY (August 2010). "Coronavirus genomics and bioinformatics analysis". Viruses. 2 (8): 1804–20. doi:10.3390/v2081803. PMC3185738. PMID 21994708. 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.
  7. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (March 2020). "The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2". Nature Microbiology. 5 (4): 536–544. doi:10.1038/s41564-020-0695-z. PMC7095448. PMID 32123347.
  8. Kohen, Jon; Kupferschmidth, Kai (28 February 2020). "Strategies shift as coronavirus pandemic looms". Science. 367 (6481): 962–963. Bibcode:2020Sci...367..962C. doi:10.1126/science.367.6481.962. PMID 32108093.
  9. Lau SK, Li KS, Huang Y, Shek CT, Tse H, Wang M, et al. (March 2010). "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 of Virology. 84 (6): 2808–19. doi:10.1128/JVI.02219-09. PMC2826035. PMID 20071579.
  10. Kieny M. "After Ebola, a Blueprint Emerges to Jump-Start R&D". Scientific American Blog Network. Archived from the original on 20 December 2016. Retrieved13 December 2016.
  11. "LIST OF PATHOGENS". World Health Organization. Archived from the original on 20 December 2016. Retrieved13 December 2016.
  12. Wong AC, Li X, Lau SK, Woo PC (February 2019). "Global Epidemiology of Bat Coronaviruses". Viruses. 11 (2): 174. doi:10.3390/v11020174. PMC6409556. PMID 30791586. See Figure 1.
  13. Woo PC, Huang Y, Lau SK, Yuen KY (August 2010). "Coronavirus genomics and bioinformatics analysis". Viruses. 2 (8): 1804–20. doi:10.3390/v2081803. PMC3185738. PMID 21994708. See Figure 1.
  14. Woo PC, Huang Y, Lau SK, Yuen KY (August 2010). "Coronavirus genomics and bioinformatics analysis". Viruses. 2 (8): 1804–20. doi:10.3390/v2081803. PMC3185738. PMID 21994708. 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.
  15. "Coronaviridae - Figures - Positive Sense RNA Viruses - Positive Sense RNA Viruses (2011)". International Committee on Taxonomy of Viruses (ICTV). Retrieved6 March 2020. See Figure 2.
  16. Gouilh MA, Puechmaille SJ, Gonzalez JP, Teeling E, Kittayapong P, Manuguerra JC (October 2011). "SARS-Coronavirus ancestor's foot-prints in South-East Asian bat colonies and the refuge theory". Infection, Genetics and Evolution. 11 (7): 1690–702. doi:10.1016/j.meegid.2011.06.021. PMC7106191. PMID 21763784. 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.
  17. Cui J, Han N, Streicker D, Li G, Tang X, Shi Z, et al. (October 2007). "Evolutionary relationships between bat coronaviruses and their hosts". Emerging Infectious Diseases. 13 (10): 1526–32. doi:10.3201/eid1310.070448. PMC2851503. PMID 18258002.
  18. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, et al. (August 2003). "Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage". Journal of Molecular Biology. 331 (5): 991–1004. doi:10.1016/S0022-2836(03)00865-9. PMC7159028. PMID 12927536. 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).
  19. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466.
  20. Fehr AR, Perlman S (2015). Maier HJ, Bickerton E, Britton P (eds.). An Overview of Their Replication and Pathogenesis; Section 2 Genomic Organization. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466.
  21. McBride R, Fielding BC (November 2012). "The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis". Viruses. 4 (11): 2902–23. doi:10.3390/v4112902. PMC3509677. PMID 23202509. See Table 1.
  22. Tang X, Li G, Vasilakis N, Zhang Y, Shi Z, Zhong Y, Wang LF, Zhang S (March 2009). "Differential stepwise evolution of SARS coronavirus functional proteins in different host species". BMC Evolutionary Biology. 9: 52. doi:10.1186/1471-2148-9-52. PMC2676248. PMID 19261195.
  23. Narayanan, Krishna; Huang, Cheng; Makino, Shinji (April 2008). "SARS coronavirus Accessory Proteins". Virus Research. 133 (1): 113–121. doi:10.1016/j.virusres.2007.10.009. ISSN 0168-1702. PMC2720074. PMID 18045721. See Table 1.
  24. McBride R, Fielding BC (November 2012). "The role of severe acute respiratory syndrome (SARS)-coronavirus accessory proteins in virus pathogenesis". Viruses. 4 (11): 2902–23. doi:10.3390/v4112902. PMC3509677. PMID 23202509.
  25. Snijder EJ, Bredenbeek PJ, Dobbe JC, Thiel V, Ziebuhr J, Poon LL, et al. (August 2003). "Unique and conserved features of genome and proteome of SARS-coronavirus, an early split-off from the coronavirus group 2 lineage". Journal of Molecular Biology. 331 (5): 991–1004. doi:10.1016/S0022-2836(03)00865-9. PMC7159028. PMID 12927536. See Figure 1.
  26. Kaina, Bernd (2021). "On the Origin of SARS-CoV-2: Did Cell Culture Experiments Lead to Increased Virulence of the Progenitor Virus for Humans?". In Vivo. 35 (3): 1313–1326. doi:10.21873/invivo.12384. PMC8193286. PMID 33910809.
  27. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H; et al. (2020). "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding". Lancet. 395 (10224): 565–574. doi:10.1016/S0140-6736(20)30251-8. PMC7159086. PMID 32007145.CS1 maint: multiple names: authors list (link)
  28. Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). "The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2". Nat Microbiol. 5 (4): 536–544. doi:10.1038/s41564-020-0695-z. PMC7095448. PMID 32123347.
  29. Kim Y, Son K, Kim YS, Lee SY, Jheong W, Oem JK (2019). "Complete genome analysis of a SARS-like bat coronavirus identified in the Republic of Korea". Virus Genes. 55 (4): 545–549. doi:10.1007/s11262-019-01668-w. PMC7089380. PMID 31076983.CS1 maint: multiple names: authors list (link)
  30. Li, W. (2005). "Bats Are Natural Reservoirs of SARS-Like Coronaviruses". Science. 310 (5748): 676–679. doi:10.1126/science.1118391. ISSN 0036-8075.
  31. Xing‐Yi Ge, Ben Hu, and Zheng‐Li Shi (2015). "BAT CORONAVIRUSES". In Lin-Fa Wang and Christopher Cowled (ed.). Bats and Viruses: A New Frontier of Emerging Infectious Diseases, First Edition. John Wiley & Sons.CS1 maint: multiple names: authors list (link)
  32. He B, Zhang Y, Xu L, Yang W, Yang F, Feng Y; et al. (2014). "Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome-like coronavirus from bats in China". J Virol. 88 (12): 7070–82. doi:10.1128/JVI.00631-14. PMC4054348. PMID 24719429.CS1 maint: multiple names: authors list (link)
  33. Lau, Susanna K. P.; Feng, Yun; Chen, Honglin; Luk, Hayes K. H.; Yang, Wei-Hong; Li, Kenneth S. M.; Zhang, Yu-Zhen; Huang, Yi; et al. (2015). "Severe Acute Respiratory Syndrome (SARS) Coronavirus ORF8 Protein Is Acquired from SARS-Related Coronavirus from Greater Horseshoe Bats through Recombination". Journal of Virology. 89 (20): 10532–10547. doi:10.1128/JVI.01048-15. ISSN 0022-538X.
  34. Xing-Yi Ge; Jia-Lu Li; Xing-Lou Yang; et al. (2013). "Isolation and characterization of a bat SARS-like coronavirus that uses the ACE2 receptor". Nature. 503 (7477): 535–8. Bibcode:2013Natur.503..535G. doi:10.1038/nature12711. PMC5389864. PMID 24172901.
  35. Yang XL, Hu B, Wang B, Wang MN, Zhang Q, Zhang W; et al. (2016). "Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus". J Virol. 90 (6): 3253–6. doi:10.1128/JVI.02582-15. PMC4810638. PMID 26719272.CS1 maint: multiple names: authors list (link)
  36. Ben, Hu; Hua, Guo; Peng, Zhou; Zheng-Li, Shi (2020). "Characteristics of SARS-CoV-2 and COVID-19". Nature Reviews Microbiology (19): 141–154. doi:10.1038/s41579-020-00459-7.
  37. Zhou H, Ji J, Chen X, Bi Y, Li J, Wang Q, et al. (June 2021). "Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses". Cell. 184 (17): 4380–4391.e14. doi:10.1016/j.cell.2021.06.008. PMC8188299. PMID 34147139.
  38. Wacharapluesadee S, Tan CW, Maneeorn P, Duengkae P, Zhu F, Joyjinda Y, et al. (February 2021). "Evidence for SARS-CoV-2 related coronaviruses circulating in bats and pangolins in Southeast Asia". Nature Communications. 12 (1): 972. Bibcode:2021NatCo..12..972W. doi:10.1038/s41467-021-21240-1. PMC7873279. PMID 33563978.
  39. Murakami S, Kitamura T, Suzuki J, Sato R, Aoi T, Fujii M, et al. (December 2020). "Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS-CoV-2, Japan". Emerging Infectious Diseases. 26 (12): 3025–3029. doi:10.3201/eid2612.203386. PMC7706965. PMID 33219796.
  40. Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC7211627. PMID 32416074.
  41. Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, et al. (July 2020). "Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins". Nature. 583 (7815): 282–285. Bibcode:2020Natur.583..282L. doi:10.1038/s41586-020-2169-0. PMID 32218527. S2CID 214683303.
  42. Liu P, Jiang JZ, Wan XF, Hua Y, Li L, Zhou J, et al. (May 2020). "Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?". PLOS Pathogens. 16 (5): e1008421. doi:10.1371/journal.ppat.1008421. PMC7224457. PMID 32407364.
  43. Hul V, Delaune D, Karlsson EA, Hassanin A, Tey PO, Baidaliuk A, et al. (26 January 2021). "A novel SARS-CoV-2 related coronavirus in bats from Cambodia". bioRxiv10.1101/2021.01.26.428212.
  44. Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, et al. (June 2020). "A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein". Current Biology. 30 (11): 2196–2203.e3. doi:10.1016/j.cub.2020.05.023. PMC7211627. PMID 32416074.
  45. Sonnevend, Julia (December 2020). Alexander, Jeffrey C.; Jacobs, Ronald N.; Smith, Philip (eds.). "A virus as an icon: the 2020 pandemic in images"(PDF). American Journal of Cultural Sociology. Basingstoke: Palgrave Macmillan. 8 (3: The COVID Crisis and Cultural Sociology: Alone Together): 451–461. doi:10.1057/s41290-020-00118-7. eISSN 2049-7121. ISSN 2049-7113. PMC7537773. PMID 33042541.
  46. Goldsmith CS, Tatti KM, Ksiazek TG, Rollin PE, Comer JA, Lee WW, et al. (February 2004). "Ultrastructural characterization of SARS coronavirus". Emerging Infectious Diseases. 10 (2): 320–6. doi:10.3201/eid1002.030913. PMC3322934. PMID 15030705. Virions acquired an envelope by budding into the cisternae and formed mostly spherical, sometimes pleomorphic, particles that averaged 78 nm in diameter (Figure 1A).
  47. Neuman BW, Adair BD, Yoshioka C, Quispe JD, Orca G, Kuhn P, et al. (August 2006). "Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy". Journal of Virology. 80 (16): 7918–28. doi:10.1128/JVI.00645-06. PMC1563832. PMID 16873249. 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.
  48. Lai MM, Cavanagh D (1997). "The molecular biology of coronaviruses". Advances in Virus Research. 48: 1–100. doi:10.1016/S0065-3527(08)60286-9. ISBN 9780120398485. PMC7130985. PMID 9233431.
  49. Masters PS (1 January 2006). The molecular biology of coronaviruses. Advances in Virus Research. 66. Academic Press. pp. 193–292. doi:10.1016/S0065-3527(06)66005-3. ISBN 9780120398690. PMC7112330. PMID 16877062. Nevertheless, the interaction between S protein and receptor remains the principal, if not sole, determinant of coronavirus host species range and tissue tropism.
  50. Cui J, Li F, Shi ZL (March 2019). "Origin and evolution of pathogenic coronaviruses". Nature Reviews. Microbiology. 17 (3): 181–192. doi:10.1038/s41579-018-0118-9. PMC7097006. PMID 30531947. 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)
  51. Fehr AR, Perlman S (2015). Maier HJ, Bickerton E, Britton P (eds.). An Overview of Their Replication and Pathogenesis; Section 2 Genomic Organization. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See section: Virion Structure.
  52. Chang CK, Hou MH, Chang CF, Hsiao CD, Huang TH (March 2014). "The SARS coronavirus nucleocapsid protein--forms and functions". Antiviral Research. 103: 39–50. doi:10.1016/j.antiviral.2013.12.009. PMC7113676. PMID 24418573. See Figure 4c.
  53. Neuman BW, Kiss G, Kunding AH, Bhella D, Baksh MF, Connelly S, et al. (April 2011). "A structural analysis of M protein in coronavirus assembly and morphology". Journal of Structural Biology. 174 (1): 11–22. doi:10.1016/j.jsb.2010.11.021. PMC4486061. PMID 21130884. See Figure 10.
  54. Lal SK, ed. (2010). Molecular Biology of the SARS-Coronavirus. doi:10.1007/978-3-642-03683-5. ISBN 978-3-642-03682-8.
  55. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See section: Coronavirus Life Cycle – Attachment and Entry
  56. Simmons G, Zmora P, Gierer S, Heurich A, Pöhlmann S (December 2013). "Proteolytic activation of the SARS-coronavirus spike protein: cutting enzymes at the cutting edge of antiviral research". Antiviral Research. 100 (3): 605–14. doi:10.1016/j.antiviral.2013.09.028. PMC3889862. PMID 24121034. See Figure 2.
  57. Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pöhlmann S (January 2014). "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein". Journal of Virology. 88 (2): 1293–307. doi:10.1128/JVI.02202-13. PMC3911672. PMID 24227843. 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).
  58. Zumla A, Chan JF, Azhar EI, Hui DS, Yuen KY (May 2016). "Coronaviruses - drug discovery and therapeutic options". Nature Reviews. Drug Discovery. 15 (5): 327–47. doi:10.1038/nrd.2015.37. PMC7097181. PMID 26868298. 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.
  59. Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, et al. (October 2019). "The human coronavirus HCoV-229E S-protein structure and receptor binding". eLife. 8. doi:10.7554/eLife.51230. PMC6970540. PMID 31650956.
  60. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See Table 2.
  61. Masters PS (1 January 2006). "The molecular biology of coronaviruses". Advances in Virus Research. Academic Press. 66: 193–292. doi:10.1016/S0065-3527(06)66005-3. ISBN 9780120398690. PMC7112330. PMID 16877062. See Figure 8.
  62. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See section: Replicase Protein Expression
  63. Mehdi Moustaqil (5 June 2020). "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". bioRxiv: 2020.06.05.135699. doi:10.1101/2020.06.05.135699. S2CID 219604020.
  64. Sexton NR, Smith EC, Blanc H, Vignuzzi M, Peersen OB, Denison MR (August 2016). "Homology-Based Identification of a Mutation in the Coronavirus RNA-Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens". Journal of Virology. 90 (16): 7415–28. doi:10.1128/JVI.00080-16. PMC4984655. PMID 27279608. 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).
  65. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See section: Corona Life Cycle – Replication and Transcription
  66. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See Figure 1.
  67. 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
  68. 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
  69. Fehr AR, Perlman S (2015). "Coronaviruses: an overview of their replication and pathogenesis". In Maier HJ, Bickerton E, Britton P (eds.). Coronaviruses. Methods in Molecular Biology. 1282. Springer. pp. 1–23. doi:10.1007/978-1-4939-2438-7_1. ISBN 978-1-4939-2438-7. PMC4369385. PMID 25720466. See section: Coronavirus Life Cycle – Assembly and Release

Severe acute respiratory syndrome–related coronavirus
Severe acute respiratory syndrome related coronavirus Language Watch Edit 160 160 Redirected from SARSr CoV This article is about a species of coronavirus comprising multiple strains For the strain that causes SARS see Severe acute respiratory syndrome coronavirus 1 For the strain that causes COVID 19 see Severe acute respiratory syndrome coronavirus 2 Severe acute respiratory syndrome related coronavirus SARSr CoV or SARS CoV note 1 is a species of virus consisting of many known strains phylogenetically related to severe acute respiratory syndrome coronavirus 1 SARS CoV 1 that have been shown to possess the capability to infect humans bats and certain other mammals 2 3 These enveloped positive sense single stranded RNA viruses enter host cells by binding to the angiotensin converting enzyme 2 ACE2 receptor 4 The SARSr CoV species is a member of the genus Betacoronavirus and of the subgenus Sarbecovirus 5 6 Severe acute respiratory syndrome related coronavirusTransmission electron micrograph of SARS related coronaviruses emerging from host cells cultured in the labVirus classification unranked VirusRealm RiboviriaKingdom OrthornaviraePhylum PisuviricotaClass PisoniviricetesOrder NidoviralesFamily CoronaviridaeGenus BetacoronavirusSubgenus SarbecovirusSpecies Severe acute respiratory syndrome related coronavirusStrainsSARS CoV 1 SARS CoV 2 Bat SARS like coronavirus WIV1 Bat coronavirus RaTG13 Numerous other bat hosted strainsSynonymsSARS coronavirus SARS related coronavirus Severe acute respiratory syndrome coronavirus 1 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 7 8 There are hundreds of other strains of SARSr CoV which are only known to infect non human species bats are a major reservoir of many strains of SARSr CoV several strains have been identified in palm civets which were likely ancestors of SARS CoV 1 7 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 in 2020 with the COVID 19 pandemic 10 11 Contents 1 Classification 2 Genome 3 Phylogenetics 3 1 SARS CoV 1 related 3 2 SARS CoV 2 related 4 Morphology 5 Life cycle 5 1 Attachment and entry 5 2 Genome translation 5 3 Replication and transcription 5 4 Recombination 5 5 Assembly and release 6 See also 7 Notes 8 References 9 Further reading 10 External linksClassification EditSARS 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 ORF1 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 and SARS CoV 2 17 4 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 7 Genome Edit Genome organization and viral proteins of SARS CoV 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 SARS CoV genome proteins orf1a to orf9b Protein Function 21 22 23 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 kB and JNK Induces apoptosis and cell cycle arrest via Caspase 8 and 9 and by Bax p53 and p38 MAP kinaseorf3b P59633 Upregulates cytokines and chemokines by RUNX1b Inhibits Type I IFN production and signaling Induces apoptosis and cell cycle arrest 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 signalingorf7a 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 arrestorf7b Q7TFA1 Unknownorf8a Q7TFA0 Induces apoptosis through mitochondria pathwayorf8b Q80H93 Enhances cellular DNA synthesis also known as X5 orf9a P59595 Nucleocapsid N protein viral RNA packaging structural protein orf9b P59636 Induces apoptosisorf10 Q7TLC7 SARS specific protein 14 The functions of several of the viral proteins are known 24 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 25 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 24 SARS coronaviruses have been genetically engineered in several laboratories 26 Phylogenetics EditPhylogenetic 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 27 28 SARSr CoV Bat CoV BtKY72 Bat CoV BM48 31 SARS CoV 1 related coronavirus SARS CoV 2 related coronavirus SARS CoV 1 related Edit A phylogenetic tree based on whole genome sequences of SARS CoV 1 and related coronaviruses is SARS CoV 1 related coronavirus 16BO133 zh 82 8 to SARS CoV 1 Rhinolophus ferrumequinum North Jeolla South Korea 29 Bat SARS CoV Rf1 87 8 to SARS CoV 1 Rhinolophus ferrumequinum Yichang Hubei 30 BtCoV HKU3 87 9 to SARS CoV 1 Rhinolophus sinicus Hong kong and Guangdong 31 LYRa11 zh 90 9 to SARS CoV 1 Rhinolophus affinis Baoshan Yunnan 32 Bat SARS CoV Rp3 92 6 to SARS CoV 1 Rhinolophus pearsoni Nanning Guangxi 30 Bat SL CoV YNLF 31C 93 5 to SARS CoV 1 Rhinolophus ferrumequinum Lufeng Yunnan 33 Bat SL CoV YNLF 34C 93 5 to SARS CoV 1 Rhinolophus ferrumequinum Lufeng Yunnan 33 SHC014 CoV 95 4 to SARS CoV 1 Rhinolophus sinicus Kunming Yunnan 34 WIV1 95 6 to SARS CoV 1 Rhinolophus sinicus Kunming Yunnan 34 WIV16 96 0 to SARS CoV 1 Rhinolophus sinicus Kunming Yunnan 35 Civet SARS CoV 99 8 to SARS CoV 1 Paguma larvata market in Guangdong China 31 SARS CoV 1 SARS CoV 2 79 to SARS CoV 1 36 SARS CoV 2 related Edit A phylogenetic tree based on whole genome sequences of SARS CoV 2 and related coronaviruses is 37 38 SARS CoV 2 related coronavirus Bat Rc o319 81 to SARS CoV 2 Rhinolophus cornutus Iwate Japan 39 Bat SL ZXC21 88 to SARS CoV 2 Rhinolophus pusillus Zhoushan Zhejiang 40 Bat SL ZC45 88 to SARS CoV 2 Rhinolophus pusillus Zhoushan Zhejiang 40 Pangolin SARSr CoV GX 89 to SARS CoV 2 Manis javanica Smuggled from Southeast Asia 41 Pangolin SARSr CoV GD 91 to SARS CoV 2 Manis javanica Smuggled from Southeast Asia 42 Bat RshSTT182 92 6 to SARS CoV 2 Rhinolophus shameli Steung Treng Cambodia 43 unreliable source Bat RshSTT200 92 6 to SARS CoV 2 Rhinolophus shameli Steung Treng Cambodia 43 unreliable source Bat RacCS203 91 5 to SARS CoV 2 Rhinolophus acuminatus Chachoengsao Thailand 38 Bat RmYN02 93 3 to SARS CoV 2 Rhinolophus malayanus Mengla Yunnan 44 Bat RpYN06 94 4 to SARS CoV 2 Rhinolophus pusillus Xishuangbanna Yunnan 37 Bat RaTG13 96 1 to SARS CoV 2 Rhinolophus affinis Mojiang Yunnan SARS CoV 2 SARS CoV 1 79 to SARS CoV 2 Morphology Edit Illustration created at the Centers for Disease Control and Prevention CDC reveals ultrastructural morphology exhibited by coronaviruses note the spikes that adorn the outer surface which impart the look of a corona surrounding the virion 45 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 pleomorphic spherical particles with bulbous surface projections that form a corona around the particles in electron micrographs 46 The size of the virus particles is in the 80 90 nm range The envelope of the virus in electron micrographs appears as a distinct pair of electron dense shells 47 The viral envelope consists of a lipid bilayer where the membrane M envelope E and spike S proteins are anchored 48 The spike proteins provide the virus with its bulbous surface projections The spike protein s interaction with its complement host cell receptor is central in determining the tissue tropism infectivity and species range of the virus 49 50 Inside the envelope there is the nucleocapsid which is formed from multiple copies of the nucleocapsid N protein which are bound to the positive sense single stranded 30 kb RNA genome in a continuous beads on a string type conformation 51 52 The lipid bilayer envelope membrane proteins and nucleocapsid protect the virus when it is outside the host 53 Life cycle EditSARS related coronavirus follows the replication strategy typical of all coronaviruses 19 54 Attachment and entry Edit Coronavirus replication cycle The attachment of the SARS related coronavirus to the host cell is mediated by the spike protein and its receptor 55 The spike protein receptor binding domain RBD recognizes and attaches to the angiotensin converting enzyme 2 ACE2 receptor 4 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 56 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 L Activation of the receptor attached spike protein causes a conformational change and the subsequent fusion of the viral envelope with the endosomal wall 56 Alternatively the virus can enter the host cell directly by proteolytic cleavage of the receptor attached spike protein by the host s TMPRSS2 or TMPRSS11D serine proteases at the cell surface 57 58 In the SARS coronavirus the activation of the 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 59 Genome translation Edit Function of coronavirus nonstructural proteins nsps 60 Protein Functionnsp1 Promotes host mRNA degradation blocks host translation blocks innate immune responsensp2 Binds to prohibitin proteins unknown functionnsp3 Multidoman transmembrane protein interacts with N protein promotes cytokine expression PLPro domain cleaves polyprotein pp1ab and blocks host s innate immune response other domains unknown functionsnsp4 Transmembrane scaffold protein allows proper structure for double membrane vesicles DMVs nsp5 3CLPro cleaves polyprotein pp1abnsp6 Transmembrane scaffold protein unknown functionnsp7 Forms hexadecameric complex with nsp8 processivity clamp for RdRp nsp12 nsp8 Forms hexadecameric complex with nsp7 processivity clamp for RdRp nsp12 acts as a primasensp9 RNA binding protein RBP nsp10 nsp16 and nsp14 cofactor forms heterodimer with both stimulates 2 O MT nsp16 and ExoN nsp14 activitynsp11 Unknown functionnsp12 RNA dependent RNA polymerase RdRp nsp13 RNA helicase 5 triphosphatasensp14 N7 Methyltransferase 3 5 exoribonuclease ExoN N7 MTase adds 5 cap ExoN proofreads genomensp15 Endoribonuclease NendoU nsp16 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 55 The genome acts as a messenger RNA and the cell s ribosome 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 1 ribosomal frameshift caused by a slippery sequence UUUAAAC and a downstream RNA pseudoknot at the end of open reading frame ORF1a 61 The ribosomal frameshift allows for the continuous translation of ORF1a followed by ORF1b 62 The polyproteins contain their own proteases PLpro and 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 62 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 63 Replication and transcription Edit Model of the replicase transcriptase complex of a coronavirus RdRp for replication red ExoN for proofreading dark blue ExoN cofactor yellow RBPs to avoid secondary structure light blue RNA sliding clamp for processivity and primase domain for priming green orange and a helicase to unwind RNA downstream A number of the nonstructural replication proteins coalesce to form a multi protein replicase transcriptase complex RTC 62 The main replicase transcriptase protein is the RNA dependent RNA polymerase RdRp It is directly involved in the replication and transcription of RNA from an RNA strand The other nonstructural proteins in the complex assist in the replication and transcription process 60 The protein nsp14 is a 3 5 exoribonuclease which provides extra fidelity to the replication process The exoribonuclease provides a 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 60 The coronaviruses require the increased fidelity and processivity during RNA synthesis because of the relatively large genome size in comparison to other RNA viruses 64 One of the main functions of the replicase transcriptase complex is to transcribe the viral genome RdRp directly mediates the 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 mRNAs 65 The other important function of the replicase transcriptase complex is to replicate the viral genome RdRp directly mediates the 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 65 The replicated positive sense genomic RNA becomes the genome of the 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 66 Recombination Edit When two SARS CoV genomes 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 polymerase switches from one template to another copy choice recombination 67 Human SARS CoV appears to have had a complex history of recombination between ancestral coronaviruses that were hosted in several different animal groups 67 68 Assembly and release Edit RNA translation occurs inside the endoplasmic reticulum The viral structural proteins S E and M move along the secretory pathway into the Golgi intermediate compartment There the M proteins direct most protein protein interactions required for assembly of viruses following its binding to the nucleocapsid 69 Progeny viruses are released from the host cell by exocytosis through secretory vesicles 69 See also Edit COVID 19 portal Viruses portal Bat SARS like coronavirus WIV1 SL CoV WIV1 Bat SARS like coronavirus RsSHC014 Bat coronavirus RaTG13 Civet SARS CoVNotes Edit 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 References Edit ICTV Taxonomy history Severe acute respiratory syndrome related coronavirus International Committee on Taxonomy of Viruses ICTV Retrieved 27 January 2019 Branswell H 9 November 2015 SARS like virus in bats shows potential to infect humans study finds Stat News Retrieved 20 February 2020 Wong AC Li X Lau SK Woo PC February 2019 Global Epidemiology of Bat Coronaviruses Viruses 11 2 174 doi 10 3390 v11020174 PMC 6409556 PMID 30791586 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 a b c Ge XY Li JL Yang XL Chmura AA Zhu G Epstein JH et al November 2013 Isolation and characterization of a bat SARS like coronavirus that uses the ACE2 receptor Nature 503 7477 535 8 Bibcode 2013Natur 503 535G doi 10 1038 nature12711 PMC 5389864 PMID 24172901 Virus Taxonomy 2018 Release International Committee on Taxonomy of Viruses ICTV October 2018 Retrieved 13 January 2019 Woo PC Huang Y Lau SK Yuen KY August 2010 Coronavirus genomics and bioinformatics analysis Viruses 2 8 1804 20 doi 10 3390 v2081803 PMC 3185738 PMID 21994708 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 a b c Coronaviridae Study Group of the International Committee on Taxonomy of Viruses March 2020 The species Severe acute respiratory syndrome related coronavirus classifying 2019 nCoV and naming it SARS CoV 2 Nature Microbiology 5 4 536 544 doi 10 1038 s41564 020 0695 z PMC 7095448 PMID 32123347 Kohen Jon Kupferschmidth Kai 28 February 2020 Strategies shift as coronavirus pandemic looms Science 367 6481 962 963 Bibcode 2020Sci 367 962C doi 10 1126 science 367 6481 962 PMID 32108093 Lau SK Li KS Huang Y Shek CT Tse H Wang M et al March 2010 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 of Virology 84 6 2808 19 doi 10 1128 JVI 02219 09 PMC 2826035 PMID 20071579 Kieny M After Ebola a Blueprint Emerges to Jump Start R amp D Scientific American Blog Network Archived from the original on 20 December 2016 Retrieved 13 December 2016 LIST OF PATHOGENS World Health Organization Archived from the original on 20 December 2016 Retrieved 13 December 2016 Wong AC Li X Lau SK Woo PC February 2019 Global Epidemiology of Bat Coronaviruses Viruses 11 2 174 doi 10 3390 v11020174 PMC 6409556 PMID 30791586 See Figure 1 Woo PC Huang Y Lau SK Yuen KY August 2010 Coronavirus genomics and bioinformatics analysis Viruses 2 8 1804 20 doi 10 3390 v2081803 PMC 3185738 PMID 21994708 See Figure 1 Woo PC Huang Y Lau SK Yuen KY August 2010 Coronavirus genomics and bioinformatics analysis Viruses 2 8 1804 20 doi 10 3390 v2081803 PMC 3185738 PMID 21994708 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 Coronaviridae Figures Positive Sense RNA Viruses Positive Sense RNA Viruses 2011 International Committee on Taxonomy of Viruses ICTV Retrieved 6 March 2020 See Figure 2 Gouilh MA Puechmaille SJ Gonzalez JP Teeling E Kittayapong P Manuguerra JC October 2011 SARS Coronavirus ancestor s foot prints in South East Asian bat colonies and the refuge theory Infection Genetics and Evolution 11 7 1690 702 doi 10 1016 j meegid 2011 06 021 PMC 7106191 PMID 21763784 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 Cui J Han N Streicker D Li G Tang X Shi Z et al October 2007 Evolutionary relationships between bat coronaviruses and their hosts Emerging Infectious Diseases 13 10 1526 32 doi 10 3201 eid1310 070448 PMC 2851503 PMID 18258002 a b c Snijder EJ Bredenbeek PJ Dobbe JC Thiel V Ziebuhr J Poon LL et al August 2003 Unique and conserved features of genome and proteome of SARS coronavirus an early split off from the coronavirus group 2 lineage Journal of Molecular Biology 331 5 991 1004 doi 10 1016 S0022 2836 03 00865 9 PMC 7159028 PMID 12927536 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 a b Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 Fehr AR Perlman S 2015 Maier HJ Bickerton E Britton P eds An Overview of Their Replication and Pathogenesis Section 2 Genomic Organization Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 McBride R Fielding BC November 2012 The role of severe acute respiratory syndrome SARS coronavirus accessory proteins in virus pathogenesis Viruses 4 11 2902 23 doi 10 3390 v4112902 PMC 3509677 PMID 23202509 See Table 1 Tang X Li G Vasilakis N Zhang Y Shi Z Zhong Y Wang LF Zhang S March 2009 Differential stepwise evolution of SARS coronavirus functional proteins in different host species BMC Evolutionary Biology 9 52 doi 10 1186 1471 2148 9 52 PMC 2676248 PMID 19261195 Narayanan Krishna Huang Cheng Makino Shinji April 2008 SARS coronavirus Accessory Proteins Virus Research 133 1 113 121 doi 10 1016 j virusres 2007 10 009 ISSN 0168 1702 PMC 2720074 PMID 18045721 See Table 1 a b McBride R Fielding BC November 2012 The role of severe acute respiratory syndrome SARS coronavirus accessory proteins in virus pathogenesis Viruses 4 11 2902 23 doi 10 3390 v4112902 PMC 3509677 PMID 23202509 Snijder EJ Bredenbeek PJ Dobbe JC Thiel V Ziebuhr J Poon LL et al August 2003 Unique and conserved features of genome and proteome of SARS coronavirus an early split off from the coronavirus group 2 lineage Journal of Molecular Biology 331 5 991 1004 doi 10 1016 S0022 2836 03 00865 9 PMC 7159028 PMID 12927536 See Figure 1 Kaina Bernd 2021 On the Origin of SARS CoV 2 Did Cell Culture Experiments Lead to Increased Virulence of the Progenitor Virus for Humans In Vivo 35 3 1313 1326 doi 10 21873 invivo 12384 PMC 8193286 PMID 33910809 Lu R Zhao X Li J Niu P Yang B Wu H et al 2020 Genomic characterisation and epidemiology of 2019 novel coronavirus implications for virus origins and receptor binding Lancet 395 10224 565 574 doi 10 1016 S0140 6736 20 30251 8 PMC 7159086 PMID 32007145 CS1 maint multiple names authors list link Coronaviridae Study Group of the International Committee on Taxonomy of Viruses 2020 The species Severe acute respiratory syndrome related coronavirus classifying 2019 nCoV and naming it SARS CoV 2 Nat Microbiol 5 4 536 544 doi 10 1038 s41564 020 0695 z PMC 7095448 PMID 32123347 Kim Y Son K Kim YS Lee SY Jheong W Oem JK 2019 Complete genome analysis of a SARS like bat coronavirus identified in the Republic of Korea Virus Genes 55 4 545 549 doi 10 1007 s11262 019 01668 w PMC 7089380 PMID 31076983 CS1 maint multiple names authors list link a b Li W 2005 Bats Are Natural Reservoirs of SARS Like Coronaviruses Science 310 5748 676 679 doi 10 1126 science 1118391 ISSN 0036 8075 a b Xing Yi Ge Ben Hu and Zheng Li Shi 2015 BAT CORONAVIRUSES In Lin Fa Wang and Christopher Cowled ed Bats and Viruses A New Frontier of Emerging Infectious Diseases First Edition John Wiley amp Sons CS1 maint multiple names authors list link He B Zhang Y Xu L Yang W Yang F Feng Y et al 2014 Identification of diverse alphacoronaviruses and genomic characterization of a novel severe acute respiratory syndrome like coronavirus from bats in China J Virol 88 12 7070 82 doi 10 1128 JVI 00631 14 PMC 4054348 PMID 24719429 CS1 maint multiple names authors list link a b Lau Susanna K P Feng Yun Chen Honglin Luk Hayes K H Yang Wei Hong Li Kenneth S M Zhang Yu Zhen Huang Yi et al 2015 Severe Acute Respiratory Syndrome SARS Coronavirus ORF8 Protein Is Acquired from SARS Related Coronavirus from Greater Horseshoe Bats through Recombination Journal of Virology 89 20 10532 10547 doi 10 1128 JVI 01048 15 ISSN 0022 538X a b Xing Yi Ge Jia Lu Li Xing Lou Yang et al 2013 Isolation and characterization of a bat SARS like coronavirus that uses the ACE2 receptor Nature 503 7477 535 8 Bibcode 2013Natur 503 535G doi 10 1038 nature12711 PMC 5389864 PMID 24172901 Yang XL Hu B Wang B Wang MN Zhang Q Zhang W et al 2016 Isolation and Characterization of a Novel Bat Coronavirus Closely Related to the Direct Progenitor of Severe Acute Respiratory Syndrome Coronavirus J Virol 90 6 3253 6 doi 10 1128 JVI 02582 15 PMC 4810638 PMID 26719272 CS1 maint multiple names authors list link Ben Hu Hua Guo Peng Zhou Zheng Li Shi 2020 Characteristics of SARS CoV 2 and COVID 19 Nature Reviews Microbiology 19 141 154 doi 10 1038 s41579 020 00459 7 a b Zhou H Ji J Chen X Bi Y Li J Wang Q et al June 2021 Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS CoV 2 and related viruses Cell 184 17 4380 4391 e14 doi 10 1016 j cell 2021 06 008 PMC 8188299 PMID 34147139 a b Wacharapluesadee S Tan CW Maneeorn P Duengkae P Zhu F Joyjinda Y et al February 2021 Evidence for SARS CoV 2 related coronaviruses circulating in bats and pangolins in Southeast Asia Nature Communications 12 1 972 Bibcode 2021NatCo 12 972W doi 10 1038 s41467 021 21240 1 PMC 7873279 PMID 33563978 Murakami S Kitamura T Suzuki J Sato R Aoi T Fujii M et al December 2020 Detection and Characterization of Bat Sarbecovirus Phylogenetically Related to SARS CoV 2 Japan Emerging Infectious Diseases 26 12 3025 3029 doi 10 3201 eid2612 203386 PMC 7706965 PMID 33219796 a b Zhou H Chen X Hu T Li J Song H Liu Y et al June 2020 A Novel Bat Coronavirus Closely Related to SARS CoV 2 Contains Natural Insertions at the S1 S2 Cleavage Site of the Spike Protein Current Biology 30 11 2196 2203 e3 doi 10 1016 j cub 2020 05 023 PMC 7211627 PMID 32416074 Lam TT Jia N Zhang YW Shum MH Jiang JF Zhu HC et al July 2020 Identifying SARS CoV 2 related coronaviruses in Malayan pangolins Nature 583 7815 282 285 Bibcode 2020Natur 583 282L doi 10 1038 s41586 020 2169 0 PMID 32218527 S2CID 214683303 Liu P Jiang JZ Wan XF Hua Y Li L Zhou J et al May 2020 Are pangolins the intermediate host of the 2019 novel coronavirus SARS CoV 2 PLOS Pathogens 16 5 e1008421 doi 10 1371 journal ppat 1008421 PMC 7224457 PMID 32407364 a b Hul V Delaune D Karlsson EA Hassanin A Tey PO Baidaliuk A et al 26 January 2021 A novel SARS CoV 2 related coronavirus in bats from Cambodia bioRxiv 10 1101 2021 01 26 428212 Zhou H Chen X Hu T Li J Song H Liu Y et al June 2020 A Novel Bat Coronavirus Closely Related to SARS CoV 2 Contains Natural Insertions at the S1 S2 Cleavage Site of the Spike Protein Current Biology 30 11 2196 2203 e3 doi 10 1016 j cub 2020 05 023 PMC 7211627 PMID 32416074 Sonnevend Julia December 2020 Alexander Jeffrey C Jacobs Ronald N Smith Philip eds A virus as an icon the 2020 pandemic in images PDF American Journal of Cultural Sociology Basingstoke Palgrave Macmillan 8 3 The COVID Crisis and Cultural Sociology Alone Together 451 461 doi 10 1057 s41290 020 00118 7 eISSN 2049 7121 ISSN 2049 7113 PMC 7537773 PMID 33042541 Goldsmith CS Tatti KM Ksiazek TG Rollin PE Comer JA Lee WW et al February 2004 Ultrastructural characterization of SARS coronavirus Emerging Infectious Diseases 10 2 320 6 doi 10 3201 eid1002 030913 PMC 3322934 PMID 15030705 Virions acquired an envelope by budding into the cisternae and formed mostly spherical sometimes pleomorphic particles that averaged 78 nm in diameter Figure 1A Neuman BW Adair BD Yoshioka C Quispe JD Orca G Kuhn P et al August 2006 Supramolecular architecture of severe acute respiratory syndrome coronavirus revealed by electron cryomicroscopy Journal of Virology 80 16 7918 28 doi 10 1128 JVI 00645 06 PMC 1563832 PMID 16873249 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 Lai MM Cavanagh D 1997 The molecular biology of coronaviruses Advances in Virus Research 48 1 100 doi 10 1016 S0065 3527 08 60286 9 ISBN 9780120398485 PMC 7130985 PMID 9233431 Masters PS 1 January 2006 The molecular biology of coronaviruses Advances in Virus Research 66 Academic Press pp 193 292 doi 10 1016 S0065 3527 06 66005 3 ISBN 9780120398690 PMC 7112330 PMID 16877062 Nevertheless the interaction between S protein and receptor remains the principal if not sole determinant of coronavirus host species range and tissue tropism Cui J Li F Shi ZL March 2019 Origin and evolution of pathogenic coronaviruses Nature Reviews Microbiology 17 3 181 192 doi 10 1038 s41579 018 0118 9 PMC 7097006 PMID 30531947 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 Fehr AR Perlman S 2015 Maier HJ Bickerton E Britton P eds An Overview of Their Replication and Pathogenesis Section 2 Genomic Organization Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See section Virion Structure Chang CK Hou MH Chang CF Hsiao CD Huang TH March 2014 The SARS coronavirus nucleocapsid protein forms and functions Antiviral Research 103 39 50 doi 10 1016 j antiviral 2013 12 009 PMC 7113676 PMID 24418573 See Figure 4c Neuman BW Kiss G Kunding AH Bhella D Baksh MF Connelly S et al April 2011 A structural analysis of M protein in coronavirus assembly and morphology Journal of Structural Biology 174 1 11 22 doi 10 1016 j jsb 2010 11 021 PMC 4486061 PMID 21130884 See Figure 10 Lal SK ed 2010 Molecular Biology of the SARS Coronavirus doi 10 1007 978 3 642 03683 5 ISBN 978 3 642 03682 8 a b Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See section Coronavirus Life Cycle Attachment and Entry a b Simmons G Zmora P Gierer S Heurich A Pohlmann S December 2013 Proteolytic activation of the SARS coronavirus spike protein cutting enzymes at the cutting edge of antiviral research Antiviral Research 100 3 605 14 doi 10 1016 j antiviral 2013 09 028 PMC 3889862 PMID 24121034 See Figure 2 Heurich A Hofmann Winkler H Gierer S Liepold T Jahn O Pohlmann S January 2014 TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein Journal of Virology 88 2 1293 307 doi 10 1128 JVI 02202 13 PMC 3911672 PMID 24227843 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 Zumla A Chan JF Azhar EI Hui DS Yuen KY May 2016 Coronaviruses drug discovery and therapeutic options Nature Reviews Drug Discovery 15 5 327 47 doi 10 1038 nrd 2015 37 PMC 7097181 PMID 26868298 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 Li Z Tomlinson AC Wong AH Zhou D Desforges M Talbot PJ et al October 2019 The human coronavirus HCoV 229E S protein structure and receptor binding eLife 8 doi 10 7554 eLife 51230 PMC 6970540 PMID 31650956 a b c Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See Table 2 Masters PS 1 January 2006 The molecular biology of coronaviruses Advances in Virus Research Academic Press 66 193 292 doi 10 1016 S0065 3527 06 66005 3 ISBN 9780120398690 PMC 7112330 PMID 16877062 See Figure 8 a b c Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See section Replicase Protein Expression Mehdi Moustaqil 5 June 2020 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 bioRxiv 2020 06 05 135699 doi 10 1101 2020 06 05 135699 S2CID 219604020 Sexton NR Smith EC Blanc H Vignuzzi M Peersen OB Denison MR August 2016 Homology Based Identification of a Mutation in the Coronavirus RNA Dependent RNA Polymerase That Confers Resistance to Multiple Mutagens Journal of Virology 90 16 7415 28 doi 10 1128 JVI 00080 16 PMC 4984655 PMID 27279608 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 a b Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See section Corona Life Cycle Replication and Transcription Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See Figure 1 a b 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 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 a b Fehr AR Perlman S 2015 Coronaviruses an overview of their replication and pathogenesis In Maier HJ Bickerton E Britton P eds Coronaviruses Methods in Molecular Biology 1282 Springer pp 1 23 doi 10 1007 978 1 4939 2438 7 1 ISBN 978 1 4939 2438 7 PMC 4369385 PMID 25720466 See section Coronavirus Life Cycle Assembly and ReleaseFurther reading EditPeiris JS Lai ST Poon LL Guan Y Yam LY Lim W et al April 2003 Coronavirus as a possible cause of severe acute respiratory syndrome Lancet 361 9366 1319 25 doi 10 1016 s0140 6736 03 13077 2 PMC 7112372 PMID 12711465 Rota PA Oberste MS Monroe SS Nix WA Campagnoli R Icenogle JP et al May 2003 Characterization of a novel coronavirus associated with severe acute respiratory syndrome Science 300 5624 1394 9 Bibcode 2003Sci 300 1394R doi 10 1126 science 1085952 PMID 12730500 Marra MA Jones SJ Astell CR Holt RA Brooks Wilson A Butterfield YS et al May 2003 The Genome sequence of the SARS associated coronavirus Science 300 5624 1399 404 Bibcode 2003Sci 300 1399M doi 10 1126 science 1085953 PMID 12730501 Snijder EJ Bredenbeek PJ Dobbe JC Thiel V Ziebuhr J Poon LL et al August 2003 Unique and conserved features of genome and proteome of SARS coronavirus an early split off from the coronavirus group 2 lineage Journal of Molecular Biology 331 5 991 1004 CiteSeerX 10 1 1 319 7007 doi 10 1016 S0022 2836 03 00865 9 PMC 7159028 PMID 12927536 S2CID 14974326 Yount B Roberts RS Lindesmith L Baric RS August 2006 Rewiring the severe acute respiratory syndrome coronavirus SARS CoV transcription circuit engineering a recombination resistant genome Proceedings of the National Academy of Sciences of the United States of America 103 33 12546 51 Bibcode 2006PNAS 10312546Y doi 10 1073 pnas 0605438103 PMC 1531645 PMID 16891412 Thiel V ed 2007 Coronaviruses Molecular and Cellular Biology 1st ed Caister Academic Press ISBN 978 1 904455 16 5 Enjuanes L Sola I Zuniga S Almazan F 2008 Coronavirus Replication and Interaction with Host In Mettenleiter TC Sobrino F eds Animal Viruses Molecular Biology Caister Academic Press ISBN 978 1 904455 22 6 External links Edit Media related to Severe acute respiratory syndrome related coronavirus at Wikimedia Commons Data related to Severe acute respiratory syndrome related coronavirus at Wikispecies WHO press release identifying and naming the SARS virus The SARS virus genetic map Science special on the SARS virus free content no registration required McGill University SARS Resources at the Wayback Machine archived 1 March 2005 U S Centers for Disease Control and Prevention CDC SARS home World Health Organization on alert Retrieved from https en wikipedia org w index php title Severe acute respiratory syndrome related coronavirus amp oldid 1045106536, wikipedia, wiki, book,

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