ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies.
Science
; 377(6607): 735-742, 2022 08 12.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1949931
ABSTRACT
The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind to all human-infecting coronavirus spike proteins from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide and acquire affinity and breadth through somatic mutations. Despite targeting a conserved motif, only some mAbs show broad neutralizing activity in vitro against alpha- and betacoronaviruses, including animal coronaviruses WIV-1 and PDF-2180. Two selected mAbs also neutralize Omicron BA.1 and BA.2 authentic viruses and reduce viral burden and pathology in vivo. Structural and functional analyses showed that the fusion peptide-specific mAbs bound with different modalities to a cryptic epitope hidden in prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme 2 (ACE2) or ACE2-mimicking mAbs.
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Glicoproteína de la Espiga del Coronavirus
/
Anticuerpos ampliamente neutralizantes
/
Enzima Convertidora de Angiotensina 2
/
SARS-CoV-2
/
COVID-19
/
Anticuerpos Monoclonales
/
Anticuerpos Antivirales
Tipo de estudio:
Ensayo controlado aleatorizado
Tópicos:
Variantes
Límite:
Animales
/
Humanos
Idioma:
Inglés
Revista:
Science
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
Science.abq2679
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