7VIC

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

7VIC の概要

• エントリーDOI: 10.2210/pdb7vic/pdb
• 分子名称: 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)
• 機能のキーワード: sars-cov-2, inhibitor, 3clpro, virus, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34192.00

構造登録者

Zhong, B.,Chen, B.,Zhou, H.,Sun, L. (登録日: 2021-09-26, 公開日: 2022-03-30, 最終更新日: 2023-11-29)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.1 Å)