Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode.
Biochemistry
; 60(39): 2925-2931, 2021 10 05.
Article
en En
| MEDLINE
| ID: mdl-34506130
ABSTRACT
Rupintrivir targets the 3C cysteine proteases of the picornaviridae family, which includes rhinoviruses and enteroviruses that cause a range of human diseases. Despite being a pan-3C protease inhibitor, rupintrivir activity is extremely weak against the homologous 3C-like protease of SARS-CoV-2. In this study, the crystal structures of rupintrivir were determined bound to enterovirus 68 (EV68) 3C protease and the 3C-like main protease (Mpro) from SARS-CoV-2. While the EV68 3C protease-rupintrivir structure was similar to previously determined complexes with other picornavirus 3C proteases, rupintrivir bound in a unique conformation to the active site of SARS-CoV-2 Mpro splitting the catalytic cysteine and histidine residues. This bifurcation of the catalytic dyad may provide a novel approach for inhibiting cysteine proteases.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antivirales
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Fenilalanina
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Pirrolidinonas
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Valina
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Inhibidores de Cisteína Proteinasa
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Proteasas 3C de Coronavirus
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SARS-CoV-2
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Isoxazoles
Idioma:
En
Revista:
Biochemistry
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos