7L0D

SARS-CoV-2 Main Protease (Mpro) in Complex with ML188

Summary for 7L0D

• Entry DOI: 10.2210/pdb7l0d/pdb
• Descriptor: 3C-like proteinase, N-[(1R)-2-(tert-butylamino)-2-oxo-1-(pyridin-3-yl)ethyl]-N-(4-tert-butylphenyl)furan-2-carboxamide (3 entities in total)
• Functional Keywords: sars-cov-2, covid19 protease, protease inhibitor, complex, hydrolase inhibitor complex, hydrolase, hydrolase-hydrolase inhibitor complex, 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: 34259.09

Authors

Lockbaum, G.J.,Lee, J.M.,Reyes, A.C.,Nalivaika, E.A.,Ali, A.,Yilmaz, N.K.,Thompson, P.R.,Schiffer, C.A. (deposition date: 2020-12-11, release date: 2021-02-10, Last modification date: 2023-10-18)

Primary citation

Lockbaum, G.J.,Reyes, A.C.,Lee, J.M.,Tilvawala, R.,Nalivaika, E.A.,Ali, A.,Kurt Yilmaz, N.,Thompson, P.R.,Schiffer, C.A.
Crystal Structure of SARS-CoV-2 Main Protease in Complex with the Non-Covalent Inhibitor ML188.
Viruses, 13:-, 2021

PubMed Abstract: Viral proteases are critical enzymes for the maturation of many human pathogenic viruses and thus are key targets for direct acting antivirals (DAAs). The current viral pandemic caused by SARS-CoV-2 is in dire need of DAAs. The Main protease (M) is the focus of extensive structure-based drug design efforts which are mostly covalent inhibitors targeting the catalytic cysteine. ML188 is a non-covalent inhibitor designed to target SARS-CoV-1 M, and provides an initial scaffold for the creation of effective pan-coronavirus inhibitors. In the current study, we found that ML188 inhibits SARS-CoV-2 M at 2.5 µM, which is more potent than against SAR-CoV-1 M. We determined the crystal structure of ML188 in complex with SARS-CoV-2 M to 2.39 Å resolution. Sharing 96% sequence identity, structural comparison of the two complexes only shows subtle differences. Non-covalent protease inhibitors complement the design of covalent inhibitors against SARS-CoV-2 main protease and are critical initial steps in the design of DAAs to treat CoVID 19.

PubMed: 33503819
DOI: 10.3390/v13020174

Experimental method

X-RAY DIFFRACTION (2.39 Å)