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COVID -19 (Novel SARS-COV-2) Genomics

Himali Meshram
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09 Apr, 2020

COVID-19 pandemic is caused by novel corona virus SARS-CoV-2. SARS-CoV-2 is enveloped single stranded RNA beta coronavirus of family coronaviridae. It is a 29.9 kB RNA genome. It shares 97 % resemblance to the bat coronavirus Ratg13 but an important difference being four aminoacid insertion at S1/S2 cleavage site. Bats like Rhinolophus affinis may serve the natural reservoir of novel corona virus 2019. It is still not clear which animals serve as intermediate hosts that brought bat corona virus to human hosts. CD4+ Tcells class II MHC axis is more important to recognise the virus and clear it by host immune system. Genetically its genome is very similar to SARS-CoV, both have four typical structural proteins but differ in 3’ open reading frames (ORF). At 3’ end of the viral genome 13 Orfs are expressed including four structural proteins- Spike (S), Envelope (E), Membrane (M) and nucleocapsid (N) and nine accessory factors. The structural proteins form capsid and envelop of the virus and non structural proteins (nsps) like nsp3,nsp5, nsp12,nsp14 and nsp16 are associated with enzymatic activities of the virus like replication and translation.Spike proteins form the outermost component of the virion particle and is responsible to recognise angiotensin converting enzyme (ACE 2) which is a transmembrae receptor on mammalian hosts utilised by coronavirus to enter host cells.Thus spike protein largely determines the host specificity and infectivity of coronavirus.Another protein, transmembrane protease serine 2 (TMPRSS2) cleaves protein S at the S1/S2 and the S2sitesand allows cellular and viral membrane fusion. Both ACE2 and TMPRSS2 are important for SARS-CoV 2 entry into host cells.In a study it was found that genetic variations in TMPRSS2 caused frequency differences between East Asians and Italians. Higher levels of TMPRSS are induced more frequently in Italian than East Asian population possibly related to higher susceptibility in Italians and Europeans. Different population may exhibit different susceptibility to this virus.Also the risk of deaths increases with increasing age. Hence if a population infected in a country is older as compared to other as seen in Italy, the case fatality rate will be higher.It is unclear whether genomic variability of major clades of SARS-CoV 2 and their geographic distribution could explain different rates of mortality worldwide.

REFERENCES

1. Protein Structure and Sequence Reanalysis of 2019-nCoV Genome Refutes Snakes as Its Intermediate Host and the Unique Similarity between Its Spike Protein Insertions and HIV-1.Zhang C, Zheng W, Huang X, Bell EW, Zhou X, Zhang Y.J Proteome Res. 2020 Apr 3;19(4):1351-1360.

2. https://www.biorxiv.org/content/biorxiv/early/ 2020/03/23/2020.02.08.939553.full.pdf

3. https://www.biorxiv.org/content/biorxiv/early/ 2020/03/24/2020.03.22.002204.full.pdf

4. https://www.biorxiv.org/content/biorxiv/early/ 2020/03/23/2020.01.29.925354.full.pdf

COVID -19 (Novel SARS-COV-2) Genomics

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