An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.
Science
; 370(6523): 1473-1479, 2020 12 18.
Article
em En
| MEDLINE
| ID: mdl-33154106
ABSTRACT
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus enters host cells via an interaction between its Spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2). By screening a yeast surface-displayed library of synthetic nanobody sequences, we developed nanobodies that disrupt the interaction between Spike and ACE2. Cryo-electron microscopy (cryo-EM) revealed that one nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains locked into their inaccessible down state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains function after aerosolization, lyophilization, and heat treatment, which enables aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Neutralizantes
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Anticorpos de Domínio Único
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Glicoproteína da Espícula de Coronavírus
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Anticorpos Antivirais
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article