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
in English
| MEDLINE | ID: covidwho-1402014
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Phenylalanine
/
Pyrrolidinones
/
Valine
/
Cysteine Proteinase Inhibitors
/
Coronavirus 3C Proteases
/
SARS-CoV-2
/
Isoxazoles
Language:
English
Journal:
Biochemistry
Year:
2021
Document Type:
Article
Affiliation country:
Acs.biochem.1c00414
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