Open AccessFunctional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein
Author(s) -
Prerna Arora,
Anzhalika Sidarovich,
Luise Graichen,
Bojan F. Hörnich,
Alexander S. Hahn,
Markus Hoffmann,
Stefan Pöhlmann
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0265453
Subject(s) - biology , tropism , mutation , coronavirus , genetics , viral entry , infectivity , microbiology and biotechnology , virus , gene , covid-19 , viral replication , medicine , disease , pathology , infectious disease (medical specialty)
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.