7VIC

The crystal structure of SARS-CoV-2 3C-like protease in complex with a traditional Chinese Medicine Inhibitors

Summary for 7VIC

• Entry DOI: 10.2210/pdb7vic/pdb
• Descriptor: 3C-like proteinase, (1beta,6beta,7beta,8alpha,9beta,10alpha,13alpha,14R,16beta)-1,6,7,14-tetrahydroxy-7,20-epoxykauran-15-one (3 entities in total)
• Functional Keywords: sars-cov-2, inhibitor, 3clpro, virus, viral protein
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• Total number of polymer chains: 1
• Total formula weight: 34192.00

Authors

Zhong, B.,Chen, B.,Zhou, H.,Sun, L. (deposition date: 2021-09-26, release date: 2022-03-30, Last modification date: 2023-11-29)

Primary citation

Zhong, B.,Peng, W.,Du, S.,Chen, B.,Feng, Y.,Hu, X.,Lai, Q.,Liu, S.,Zhou, Z.W.,Fang, P.,Wu, Y.,Gao, F.,Zhou, H.,Sun, L.
Oridonin Inhibits SARS-CoV-2 by Targeting Its 3C-Like Protease.
Small Sci, 2:2100124-2100124, 2022

PubMed Abstract: The current COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an enormous threat to public health. The SARS-CoV-2 3C-like protease (3CLpro), which is critical for viral replication and transcription, has been recognized as an ideal drug target. Herein, it is identified that three herbal compounds, Salvianolic acid A (SAA), (-)-Epigallocatechin gallate (EGCG), and Oridonin, directly inhibit the activity of SARS-CoV-2 3CLpro. Further, blocking SARS-CoV-2 infectivity by Oridonin is confirmed in cell-based experiments. By solving the crystal structure of 3CLpro in complex with Oridonin and comparing it to that of other ligands with 3CLpro, it is identified that Oridonin binds at the 3CLpro catalytic site by forming a C-S covalent bond, which is confirmed by mass spectrometry and kinetic study, blocking substrate binding through a nonpeptidomimetic covalent binding mode. Thus, Oridonin is a novel candidate to develop a new antiviral treatment for COVID-19.

PubMed: 35600064
DOI: 10.1002/smsc.202100124

Experimental method

X-RAY DIFFRACTION (2.1 Å)