Determinants of Spike infectivity, processing, and neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2.
Cell Host Microbe
; 30(9): 1255-1268.e5, 2022 09 14.
Article
em En
| MEDLINE
| ID: mdl-35931073
ABSTRACT
SARS-CoV-2 Omicron rapidly outcompeted other variants and currently dominates the COVID-19 pandemic. Its enhanced transmission and immune evasion are thought to be driven by numerous mutations in the Omicron Spike protein. Here, we systematically introduced BA.1 and/or BA.2 Omicron Spike mutations into the ancestral Spike protein and examined the impacts on Spike function, processing, and susceptibility to neutralization. Individual mutations of S371F/L, S375F, and T376A in the ACE2-receptor-binding domain as well as Q954H and N969K in the hinge region 1 impaired infectivity, while changes to G339D, D614G, N764K, and L981F moderately enhanced it. Most mutations in the N-terminal region and receptor-binding domain reduced the sensitivity of the Spike protein to neutralization by sera from individuals vaccinated with the BNT162b2 vaccine and by therapeutic antibodies. Our results represent a systematic functional analysis of Omicron Spike adaptations that have allowed this SARS-CoV-2 variant to dominate the current pandemic.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteína da Espícula de Coronavírus
/
SARS-CoV-2
/
COVID-19
Limite:
Humans
Idioma:
En
Revista:
Cell Host Microbe
Assunto da revista:
MICROBIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Alemanha