7L8J

SARS-CoV-2 Main Protease (Mpro) in Complex with Rupintrivir (P21212)

Summary for 7L8J

• Entry DOI: 10.2210/pdb7l8j/pdb
• Descriptor: 3C-like proteinase, 4-{2-(4-FLUORO-BENZYL)-6-METHYL-5-[(5-METHYL-ISOXAZOLE-3-CARBONYL)-AMINO]-4-OXO-HEPTANOYLAMINO}-5-(2-OXO-PYRROLIDIN-3-YL)-PENTANOIC ACID ETHYL ESTER (3 entities in total)
• Functional Keywords: sars-cov-2, sars2, covid19, protease, protease inhibitor, complex, hydrolase inhibitor complex, hydrolase, hydrolase-hydrolase inhibitor complex, rupintrivir, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2, COVID-19 virus)
• Total number of polymer chains: 1
• Total formula weight: 34426.22

Authors

Lockbaum, G.J.,Henes, M.,Lee, J.M.,Timm, J.,Nalivaika, E.A.,Yilmaz, N.K.,Thompson, P.R.,Schiffer, C.A. (deposition date: 2020-12-31, release date: 2021-09-22, Last modification date: 2024-10-09)

Primary citation

Lockbaum, G.J.,Henes, M.,Lee, J.M.,Timm, J.,Nalivaika, E.A.,Thompson, P.R.,Kurt Yilmaz, N.,Schiffer, C.A.
Pan-3C Protease Inhibitor Rupintrivir Binds SARS-CoV-2 Main Protease in a Unique Binding Mode.
Biochemistry, 60:2925-2931, 2021

PubMed 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 (M) 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 M splitting the catalytic cysteine and histidine residues. This bifurcation of the catalytic dyad may provide a novel approach for inhibiting cysteine proteases.

PubMed: 34506130
DOI: 10.1021/acs.biochem.1c00414

Experimental method

X-RAY DIFFRACTION (2.45 Å)