Functional and antigenic characterization of SARS-CoV-2 spike fusion peptide by deep mutational scanning.
Nat Commun
; 15(1): 4056, 2024 May 14.
Article
en En
| MEDLINE
| ID: mdl-38744813
ABSTRACT
The fusion peptide of SARS-CoV-2 spike protein is functionally important for membrane fusion during virus entry and is part of a broadly neutralizing epitope. However, sequence determinants at the fusion peptide and its adjacent regions for pathogenicity and antigenicity remain elusive. In this study, we perform a series of deep mutational scanning (DMS) experiments on an S2 region spanning the fusion peptide of authentic SARS-CoV-2 in different cell lines and in the presence of broadly neutralizing antibodies. We identify mutations at residue 813 of the spike protein that reduced TMPRSS2-mediated entry with decreased virulence. In addition, we show that an F823Y mutation, present in bat betacoronavirus HKU9 spike protein, confers resistance to broadly neutralizing antibodies. Our findings provide mechanistic insights into SARS-CoV-2 pathogenicity and also highlight a potential challenge in developing broadly protective S2-based coronavirus vaccines.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Internalización del Virus
/
Anticuerpos Neutralizantes
/
Glicoproteína de la Espiga del Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Mutación
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Commun
Asunto de la revista:
BIOLOGIA
/
CIENCIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos