Severe acute respiratory syndrome-related coronavirus

Severe acute respiratory syndrome-related coronavirus (SARSr-CoV)[note 1] is a species of coronavirus known to infect humans, bats, and certain other mammals. The SARS-related coronavirus is an enveloped, positive-sense, single-stranded RNA virus. It is most closely related to group 2 coronaviruses (Betacoronavirus).

Severe acute respiratory syndrome-related coronavirus
SARS virion.gif
Electron microscope image of a SARS-CoV virion
2019-nCoV-CDC-23312 without background.png
Illustration of a SARS-CoV-2 virion
Virus classification e
(unranked): Virus
Realm: Riboviria
Phylum: incertae sedis
Order: Nidovirales
Family: Coronaviridae
Genus: Betacoronavirus
Subgenus: Sarbecovirus
Species:
Severe acute respiratory syndrome-related coronavirus
Strains

SARS-CoV
SARS-CoV-2
Bat SARS-like coronavirus WIV1
Numerous other bat strains

Synonyms
  • SARS coronavirus
  • SARS-related coronavirus
  • Severe acute respiratory syndrome coronavirus[1]

Two strains of the virus have caused outbreaks of severe respiratory diseases in humans: SARS-CoV, which caused an outbreak of severe acute respiratory syndrome (SARS) between 2002 and 2004, and SARS-CoV-2, which since late 2019 has caused an outbreak of coronavirus disease 2019 (COVID-19).[2] Both strains descended from a single ancestor but made the cross-species jump into humans separately, and SARS-CoV-2 is not a direct descendant of SARS-CoV.[2] There are hundreds of other strains of SARSr-CoV, all of which are only known to infect non-human species: bats are a major reservoir of many strains of SARS-related coronaviruses, and several strains have been identified in palm civets which were likely ancestors of SARS-CoV.[2][3]

The SARS-related coronavirus was one of several viruses identified by 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. The prediction came to pass with the 2019–20 coronavirus outbreak [4][5]

VirologyEdit

 
Scanning Electron Micrograph of SARS virions

The SARS-related coronavirus is a positive-sense single-stranded RNA virus belonging to a family of enveloped coronaviruses. Its genome is about 29.7kb, which is one of the largest among RNA viruses. The virus has 13 known genes and 14 known proteins. There are 265 nucleotides in the 5'UTR and 342 nucleotides in the 3'UTR. SARSr-CoV is similar to other coronaviruses in that its genome expression starts with translation of two large ORFs, 1a and 1b, both of which are polyproteins.

The functions of several of these proteins are known:[6] ORFs 1a and 1b encode the replicase and there are four major structural proteins: nucleocapsid, spike, membrane and envelope. It also encodes for eight unique proteins, known as the accessory proteins, all with no known homologues. The function of these accessory proteins remains unknown.[6]

Coronaviruses usually express pp1a (the ORF1a polyprotein) and the pp1ab polyprotein which joins ORF1a and ORF1b. The polyproteins are then processed by enzymes that are encoded by ORF1a. Product proteins from the processing includes various replicative enzymes such as RNA-dependent RNA polymerase, RNA helicase, and proteinase. The replication complex in a coronavirus is also responsible for the synthesis of various mRNAs downstream of ORF1b, which are structural and accessory proteins. Two different proteins, 3CLpro and PL2pro, cleave the large polyproteins into 16 smaller subunits.

Replication cycleEdit

SARS-related coronaviruses follows the replication strategy typical of the coronaviruses. [7][8][9][10][11]

Cell receptor attachment and membrane fusionEdit

The virus has a lipid bilayer envelope where the membrane (M), envelope (E) and spike (S) proteins are anchored. Inside is the nucleocapsid and multiple copies of the (N) protein serving as a shell for the positive-sense single-stranded (30,000 nucleotides) RNA genome. The capsid, membrane and lipid envelope protect the virus when it is outside the host.

The attachment of the virus to the host cell is mediated by the S protein and its receptor. The receptor binding domain (RBD) recognizes and attaches to the ACE2 receptor of lung epithelial cells. Following attachment the virus enters the cell which is mediated by proteolytic cleavage of the S protein by the TMPRSS2 protease. In the SARS coronavius, the C-terminal part of the S protein triggers the fusion of the viral envelope with the host cell membrane by inducing conformational changes that are not fully understood.[12] When over-expressed inside the infected cell the S protein may be secreted on the surface of the cell's membrane which will provoke a membrane fusion with the neighboring cells.

Genome translationEdit

The nucleocapsid passes into the cytoplasm where the viral genome is released. This genome acts as a messenger RNA and the cell's ribosomes translate two-thirds of the genome into two large overlapping polyproteins. They contain proteases which detach and cleave the polyproteins at various sites, obtaining about 15 proteins needed for and replication.[13]

ReplicationEdit

Viral proteins form a replicase-transcriptase polyprotein containing enzymes, among which is a RNA-dependent RNA polymerase which mediates the synthesis of negative-sense RNA molecules, which is followed by the transcription to the corresponding mRNAs and translation to two polyproteins. The two polyproteins are result of a ribosomal frame shifting. The full-length negative then positive RNA strand is synthesized that becomes the genome of the progeny viruses. The various smaller mRNAs correspond to the last third of the virus genome and are translated mainly into the structural proteins that will become part of the progeny virus particles.

AssemblyEdit

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 nucelocapsid.

ReleaseEdit

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

MorphologyEdit

The morphology of the SARSr coronavirus is characteristic of the coronavirus family as a whole. These viruses have large pleomorphic spherical particles with bulbous surface projections that form a corona around particles. The envelope of the virus contains lipid and appears to consist of a distinct pair of electron dense shells.

The internal component of the shell is a single-stranded helical ribonucleoprotein. There are also long surface projections that protrude from the lipid envelope. The size of these particles is in the 80–90 nm range.

EvolutionEdit

SARSr-CoV is most closely related to group 2 coronaviruses (Betacoronavirus), but it does not segregate into any of the other three groups of coronaviruses. A theory has been proposed that bat coronaviruses have coevolved with their hosts for a long time then jumped species from bats to humans.[14][15] The closest outgroup to the coronaviruses are the toroviruses, with which it has homology in the ORF 1b replicase and the two viron proteins of S and M. SARSr-CoV was determined to be an early split off from the group 2 coronaviruses based on a set of conserved domains that it shares with group 2.

A main difference between other group 2 coronaviruses and SARSr-CoV is the nsp3 replicase subunit encoded by ORF1a. SARSr-CoV does not have a papain-like proteinase 1.

See alsoEdit


ReferencesEdit

  1. ^ "ICTV Taxonomy history: Severe acute respiratory syndrome-related coronavirus" (html). International Committee on Taxonomy of Viruses (ICTV). Retrieved 27 January 2019.
  2. ^ a b c Coronavirus Study Group (11 February 2020). "Severe acute respiratory syndrome-related coronavirus: The species and its viruses" (PDF). bioRxiv. Retrieved 12 February 2020.
  3. ^ 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 (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.
  4. ^ Kieny, Marie-Paule. "After Ebola, a Blueprint Emerges to Jump-Start R&D". Scientific American Blog Network. Archived from the original on 20 December 2016. Retrieved 13 December 2016.
  5. ^ "LIST OF PATHOGENS". World Health Organization. Archived from the original on 20 December 2016. Retrieved 13 December 2016.
  6. ^ 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): 2902–2923. doi:10.3390/v4112902. ISSN 1999-4915. PMC 3509677. PMID 23202509.
  7. ^ Coronaviruses: An Overview of Their Replication and Pathogenesis
  8. ^ Structures and functions of Coronavirus proteins: molecular modeling of viral nucleoprotein (PDF)
  9. ^ Molecular Biology of the SARS-Coronavirus
  10. ^ Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins
  11. ^ Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China
  12. ^ Li Z, Tomlinson AC, Wong AH, Zhou D, Desforges M, Talbot PJ, Benlekbir S, Rubinstein JL, Rini JM (October 2019). "The human coronavirus HCoV-229E S-protein structure and receptor binding". eLife. 8. doi:10.7554/eLife.51230. PMC 6970540. PMID 31650956.
  13. ^ Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins
  14. ^ 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 (Oct 2007). "Evolutionary relationships between bat coronaviruses and their hosts". Emerg. Infect. Dis. 13 (10): 1526–32. doi:10.3201/eid1310.070448. PMC 2851503. PMID 18258002.
  15. ^ 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 (Nov 28, 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.

Further readingEdit

External linksEdit


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