Functional Analysis of Polymorphisms at the S1/S2 Site of SARS-CoV-2 Spike Protein

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2022 Mar 25

PMID 35333910

Authors

Prerna Arora

Anzhalika Sidarovich

Luise Graichen

Bojan Hornich

Alexander Hahn

Markus Hoffmann

Stefan Pohlmann

Affiliations

Soon will be listed here.

Abstract

Several SARS-CoV-2 variants emerged that harbor mutations in the surface unit of the viral spike (S) protein that enhance infectivity and transmissibility. Here, we analyzed whether ten naturally-occurring mutations found within the extended loop harboring the S1/S2 cleavage site of the S protein, a determinant of SARS-CoV-2 cell tropism and pathogenicity, impact S protein processing and function. None of the mutations increased but several decreased S protein cleavage at the S1/S2 site, including S686G and P681H, the latter of which is found in variants of concern B.1.1.7 (Alpha variant) and B.1.1.529 (Omicron variant). None of the mutations reduced ACE2 binding and cell-cell fusion although several modulated the efficiency of host cell entry. The effects of mutation S686G on viral entry were cell-type dependent and could be linked to the availability of cathepsin L for S protein activation. These results show that polymorphisms at the S1/S2 site can modulate S protein processing and host cell entry.

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