A broad and potent neutralization epitope in SARS-related coronaviruses.
Proc Natl Acad Sci U S A
; 119(29): e2205784119, 2022 07 19.
Article
en En
| MEDLINE
| ID: mdl-35767670
ABSTRACT
Many neutralizing antibodies (nAbs) elicited to ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through natural infection and vaccination have reduced effectiveness to SARS-CoV-2 variants. Here, we show that therapeutic antibody ADG20 is able to neutralize SARS-CoV-2 variants of concern (VOCs) including Omicron (B.1.1.529) as well as other SARS-related coronaviruses. We delineate the structural basis of this relatively escape-resistant epitope that extends from one end of the receptor binding site (RBS) into the highly conserved CR3022 site. ADG20 can then benefit from high potency through direct competition with ACE2 in the more variable RBS and interaction with the more highly conserved CR3022 site. Importantly, antibodies that are able to target this site generally neutralize a broad range of VOCs, albeit with reduced potency against Omicron. Thus, this conserved and vulnerable site can be exploited for the design of universal vaccines and therapeutic antibodies.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Anticuerpos Neutralizantes
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Glicoproteína de la Espiga del Coronavirus
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SARS-CoV-2
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COVID-19
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Anticuerpos Monoclonales
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Anticuerpos Antivirales
Límite:
Humans
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Año:
2022
Tipo del documento:
Article