Delta spike P681R mutation enhances SARS-CoV-2 fitness over Alpha variant.
Cell Rep
; 39(7): 110829, 2022 05 17.
Article
em En
| MEDLINE
| ID: mdl-35550680
ABSTRACT
We report that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta spike mutation P681R plays a key role in the Alpha-to-Delta variant replacement during the coronavirus disease 2019 (COVID-19) pandemic. Delta SARS-CoV-2 efficiently outcompetes the Alpha variant in human lung epithelial cells and primary human airway tissues. The Delta spike mutation P681R is located at a furin cleavage site that separates the spike 1 (S1) and S2 subunits. Reverting the P681R mutation to wild-type P681 significantly reduces the replication of the Delta variant to a level lower than the Alpha variant. Mechanistically, the Delta P681R mutation enhances the cleavage of the full-length spike to S1 and S2, which could improve cell-surface-mediated virus entry. In contrast, the Alpha spike also has a mutation at the same amino acid (P681H), but the cleavage of the Alpha spike is reduced compared with the Delta spike. Our results suggest P681R as a key mutation in enhancing Delta-variant replication via increased S1/S2 cleavage.
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Base de dados:
MEDLINE
Assunto principal:
SARS-CoV-2
/
COVID-19
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article