Intermediates in SARS-CoV-2 spike-mediated cell entry.
Sci Adv
; 8(33): eabo3153, 2022 08 19.
Article
em En
| MEDLINE
| ID: mdl-35984891
ABSTRACT
SARS-CoV-2 cell entry is completed after viral spike (S) protein-mediated membrane fusion between viral and host cell membranes. Stable prefusion and postfusion S structures have been resolved by cryo-electron microscopy and cryo-electron tomography, but the refolding intermediates on the fusion pathway are transient and have not been examined. We used an antiviral lipopeptide entry inhibitor to arrest S protein refolding and thereby capture intermediates as S proteins interact with hACE2 and fusion-activating proteases on cell-derived target membranes. Cryo-electron tomography imaged both extended and partially folded intermediate states of S2, as well as a novel late-stage conformation on the pathway to membrane fusion. The intermediates now identified in this dynamic S protein-directed fusion provide mechanistic insights that may guide the design of CoV entry inhibitors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Glicoproteína da Espícula de Coronavírus
/
SARS-CoV-2
/
COVID-19
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article