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Differentially conserved amino acid positions may reflect differences in SARS-CoV-2 and SARS-CoV behaviour

Bojkova, Denisa, McGreig, Jake E., McLaughlin, Katie-May, Masterson, Stuart G., Antczak, Magdalena, Widera, Marek, Krähling, Verena, Ciesek, Sandra, Wass, Mark N., Michaelis, Martin, and others. (2021) Differentially conserved amino acid positions may reflect differences in SARS-CoV-2 and SARS-CoV behaviour. Bioinformatics, . ISSN 1367-4803. E-ISSN 1460-2059. (doi:10.1093/bioinformatics/btab094) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided) (KAR id:86834)

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https://doi.org/10.1093/bioinformatics%2Fbtab094

Abstract

Motivation: SARS-CoV-2 is a novel coronavirus currently causing a pandemic. Here, we per-formed a combined in-silico and cell culture comparison of SARS-CoV-2 and the closely related SARS-CoV.Results: Many amino acid positions are differentially conserved between SARS-CoV-2 and SARS-CoV, which reflects the discrepancies in virus behaviour, i.e. more effective human-to-human transmission of SARS-CoV-2 and higher mortality associated with SARS-CoV. Variations in the S protein (mediates virus entry) were associated with differences in its interaction with ACE2 (cellular S receptor) and sensitivity to TMPRSS2 (enables virus entry via S cleavage) inhi-bition. Anti-ACE2 antibodies more strongly inhibited SARS-CoV than SARS-CoV-2 infection, probably due to a stronger SARS-CoV-2 S-ACE2 affinity relative to SARS-CoV S. Moreover, SARS-CoV-2 and SARS-CoV displayed differences in cell tropism. Cellular ACE2 and TMPRSS2 levels did not indicate susceptibility to SARS-CoV-2. In conclusion, we identified genomic varia-tion between SARS-CoV-2 and SARS-CoV that may reflect the differences in their clinical and biological behaviour.

Item Type: Article
DOI/Identification number: 10.1093/bioinformatics/btab094
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > Biosciences
Depositing User: Mark Wass
Date Deposited: 01 Mar 2021 09:25 UTC
Last Modified: 07 May 2021 07:31 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/86834 (The current URI for this page, for reference purposes)
Antczak, Magdalena: https://orcid.org/0000-0003-1503-1849
Wass, Mark N.: https://orcid.org/0000-0001-5428-6479
Michaelis, Martin: https://orcid.org/0000-0002-5710-5888
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