Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice.
Proc Natl Acad Sci U S A
; 118(19)2021 05 11.
Article
em En
| MEDLINE
| ID: mdl-33893175
ABSTRACT
Neutralizing antibodies are important for immunity against SARS-CoV-2 and as therapeutics for the prevention and treatment of COVID-19. Here, we identified high-affinity nanobodies from alpacas immunized with coronavirus spike and receptor-binding domains (RBD) that disrupted RBD engagement with the human receptor angiotensin-converting enzyme 2 (ACE2) and potently neutralized SARS-CoV-2. Epitope mapping, X-ray crystallography, and cryo-electron microscopy revealed two distinct antigenic sites and showed two neutralizing nanobodies from different epitope classes bound simultaneously to the spike trimer. Nanobody-Fc fusions of the four most potent nanobodies blocked ACE2 engagement with RBD variants present in human populations and potently neutralized both wild-type SARS-CoV-2 and the N501Y D614G variant at concentrations as low as 0.1 nM. Prophylactic administration of either single nanobody-Fc or as mixtures reduced viral loads by up to 104-fold in mice infected with the N501Y D614G SARS-CoV-2 virus. These results suggest a role for nanobody-Fc fusions as prophylactic agents against SARS-CoV-2.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Anticorpos Neutralizantes
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Anticorpos de Domínio Único
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SARS-CoV-2
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COVID-19
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Tratamento Farmacológico da COVID-19
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Anticorpos Antivirais
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article