Structural mechanism of SARS-CoV-2 neutralization by two murine antibodies targeting the RBD.
Cell Rep
; 37(4): 109881, 2021 10 26.
Article
em En
| MEDLINE
| ID: mdl-34655519
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has necessitated the rapid development of antibody-based therapies and vaccines as countermeasures. Here, we use cryoelectron microscopy (cryo-EM) to characterize two protective anti-SARS-CoV-2 murine monoclonal antibodies (mAbs) in complex with the spike protein, revealing similarities between epitopes targeted by human and murine B cells. The more neutralizing mAb, 2B04, binds the receptor-binding motif (RBM) of the receptor-binding domain (RBD) and competes with angiotensin-converting enzyme 2 (ACE2). By contrast, 2H04 binds adjacent to the RBM and does not compete for ACE2 binding. Naturally occurring sequence variants of SARS-CoV-2 and corresponding neutralization escape variants selected in vitro map to our structurally defined epitopes, suggesting that SARS-CoV-2 might evade therapeutic antibodies with a limited set of mutations, underscoring the importance of combination mAb therapeutics. Finally, we show that 2B04 neutralizes SARS-CoV-2 infection by preventing ACE2 engagement, whereas 2H04 reduces host cell attachment without directly disrupting ACE2-RBM interactions, providing distinct inhibitory mechanisms used by RBD-specific mAbs.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Neutralizantes
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Glicoproteína da Espícula de Coronavírus
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SARS-CoV-2
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COVID-19
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Anticorpos Antivirais
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos