7MRR

Crystal Structure of SARS-CoV-2 Main Protease (3CLpro/Mpro) in Complex with Covalent Inhibitor Leupeptin

Summary for 7MRR

• Entry DOI: 10.2210/pdb7mrr/pdb
• Related: 7JYC 7K3T 7K40 7K6D 7K6E 7MNG
• Related PRD ID: PRD_000216
• Descriptor: 3C-like proteinase, LEUPEPTIN, DIMETHYL SULFOXIDE, ... (4 entities in total)
• Functional Keywords: sars-cov-2, main protease, 3clpro/mpro, leupeptin, viral protein, inhibitor, hydrolase-inhibitor complex, hydrolase/inhibitor
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 2
• Total formula weight: 34567.66

Authors

Andi, B.,Kumaran, D.,Soares, A.S.,Kreitler, D.F.,Shi, W.,Jakoncic, J.,Fuchs, M.R.,Keereetaweep, J.,Shanklin, J.,McSweeney, S. (deposition date: 2021-05-08, release date: 2021-05-19, Last modification date: 2024-10-30)

Primary citation

Andi, B.,Kumaran, D.,Kreitler, D.F.,Soares, A.S.,Keereetaweep, J.,Jakoncic, J.,Lazo, E.O.,Shi, W.,Fuchs, M.R.,Sweet, R.M.,Shanklin, J.,Adams, P.D.,Schmidt, J.G.,Head, M.S.,McSweeney, S.
Hepatitis C virus NS3/4A inhibitors and other drug-like compounds as covalent binders of SARS-CoV-2 main protease.
Sci Rep, 12:12197-12197, 2022

PubMed Abstract: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), threatens global public health. The world needs rapid development of new antivirals and vaccines to control the current pandemic and to control the spread of the variants. Among the proteins synthesized by the SARS-CoV-2 genome, main protease (M also known as 3CL) is a primary drug target, due to its essential role in maturation of the viral polyproteins. In this study, we provide crystallographic evidence, along with some binding assay data, that three clinically approved anti hepatitis C virus drugs and two other drug-like compounds covalently bind to the M Cys145 catalytic residue in the active site. Also, molecular docking studies can provide additional insight for the design of new antiviral inhibitors for SARS-CoV-2 using these drugs as lead compounds. One might consider derivatives of these lead compounds with higher affinity to the M as potential COVID-19 therapeutics for further testing and possibly clinical trials.

PubMed: 35842458
DOI: 10.1038/s41598-022-15930-z

Experimental method

X-RAY DIFFRACTION (2.32 Å)