Spike substitution T813S increases Sarbecovirus fusogenicity by enhancing the usage of TMPRSS2.
PLoS Pathog
; 19(5): e1011123, 2023 05.
Article
in English
| MEDLINE | ID: covidwho-2324624
ABSTRACT
SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Severe acute respiratory syndrome-related coronavirus
/
COVID-19
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
PLoS Pathog
Year:
2023
Document Type:
Article
Affiliation country:
Journal.ppat.1011123
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