Functional analysis of polymorphisms at the S1/S2 site of SARS-CoV-2 spike protein.
PLoS One
; 17(3): e0265453, 2022.
Article
in English
| MEDLINE | ID: covidwho-1855002
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
Topics:
Variants
Limits:
Animals
/
Humans
Language:
English
Journal:
PLoS One
Journal subject:
Science
/
Medicine
Year:
2022
Document Type:
Article
Affiliation country:
Journal.pone.0265453
Similar
MEDLINE
...
LILACS
LIS