Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses

Cotten, M. , Robertson, D. L. and Phan, M. V.T. (2021) Unique protein features of SARS-CoV-2 relative to other Sarbecoviruses. Virus Evolution, 7(2), veab067. (doi: 10.1093/ve/veab067) (PMID:34527286) (PMCID:PMC8385934)

Abstract

Defining the unique properties of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein sequences has potential to explain the range of Coronavirus Disease 2019 severity. To achieve this we compared proteins encoded by all Sarbecoviruses using profile Hidden Markov Model similarities to identify protein features unique to SARS-CoV-2. Consistent with previous reports, a small set of bat- and pangolin-derived Sarbecoviruses show the greatest similarity to SARS-CoV-2 but are unlikely to be the direct source of SARS-CoV-2. Three proteins (nsp3, spike, and orf9) showed regions differing between the bat Sarbecoviruses and SARS-CoV-2 and indicate virus protein features that might have evolved to support human infection and/or transmission. Spike analysis identified all regions of the protein that have tolerated change and revealed that the current SARS-CoV-2 variants of concern have sampled only a fraction (∼31 per cent) of the possible spike domain changes which have occurred historically in Sarbecovirus evolution. This result emphasises the evolvability of these coronaviruses and the potential for further change in virus replication and transmission properties over the coming years.

• Item Type: Articles
• Additional Information: This work was supported by the Wellcome, DFID—Wellcome Epidemic Preparedness—Coronavirus (AFRICO19, grant agreement number 220977/Z/20/Z) awarded to M.C. D.L.R. and M.C. Funding for open access charge: MRC (MC_UU_1201412), by the UK Medical Research Council (MRC/UKRI) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement (grant agreement number NC_PC_19060).
• Keywords: SARS-CoV-2, proteome changes, Sarbecovirus evolution, spike protein changes.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Robertson, Professor David and Cotten, Professor Matthew
• Authors: Cotten, M., Robertson, D. L., and Phan, M. V.T.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Virus Evolution
• Publisher: Oxford University Press
• ISSN: 2057-1577
• ISSN (Online): 2057-1577
• Published Online: 23 July 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Virus Evolution 7(2): veab067
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
		Viral Genomics and Bioinformatics	Andrew Davison	Medical Research Council (MRC)	MC_UU_12014/12	III-MRC-GU Centre for Virus Research