Structural basis for broad coronavirus neutralization.
Nat Struct Mol Biol
; 28(6): 478-486, 2021 06.
Article
em En
| MEDLINE
| ID: mdl-33981021
ABSTRACT
Three highly pathogenic ß-coronaviruses have crossed the animal-to-human species barrier in the past two decades SARS-CoV, MERS-CoV and SARS-CoV-2. To evaluate the possibility of identifying antibodies with broad neutralizing activity, we isolated a monoclonal antibody, termed B6, that cross-reacts with eight ß-coronavirus spike glycoproteins, including all five human-infecting ß-coronaviruses. B6 broadly neutralizes entry of pseudotyped viruses from lineages A and C, but not from lineage B, and the latter includes SARS-CoV and SARS-CoV-2. Cryo-EM, X-ray crystallography and membrane fusion assays reveal that B6 binds to a conserved cryptic epitope located in the fusion machinery. The data indicate that antibody binding sterically interferes with the spike conformational changes leading to membrane fusion. Our data provide a structural framework explaining B6 cross-reactivity with ß-coronaviruses from three lineages, along with a proof of concept for antibody-mediated broad coronavirus neutralization elicited through vaccination. This study unveils an unexpected target for next-generation structure-guided design of a pan-ß-coronavirus vaccine.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções por Coronavirus
/
Anticorpos Neutralizantes
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Glicoproteína da Espícula de Coronavírus
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Betacoronavirus
/
Anticorpos Monoclonais
/
Anticorpos Antivirais
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Struct Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos