7EN8

Crystal structure of SARS-CoV-2 3CLpro in complex with the non-covalent inhibitor WU-04

7EN8 の概要

• エントリーDOI: 10.2210/pdb7en8/pdb
• 分子名称: 3C-like proteinase, ~{N}-[(1~{S},2~{R})-2-[[4-bromanyl-2-(methylcarbamoyl)-6-nitro-phenyl]amino]cyclohexyl]isoquinoline-4-carboxamide, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: non-covalent, inhibitor, 3clpro, coronavirus, 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: 2
• 化学式量合計: 68795.95

構造登録者

Hou, N.,Peng, C.,Hu, Q. (登録日: 2021-04-16, 公開日: 2022-07-20, 最終更新日: 2023-11-29)

主引用文献

Hou, N.,Shuai, L.,Zhang, L.,Xie, X.,Tang, K.,Zhu, Y.,Yu, Y.,Zhang, W.,Tan, Q.,Zhong, G.,Wen, Z.,Wang, C.,He, X.,Huo, H.,Gao, H.,Xu, Y.,Xue, J.,Peng, C.,Zou, J.,Schindewolf, C.,Menachery, V.,Su, W.,Yuan, Y.,Shen, Z.,Zhang, R.,Yuan, S.,Yu, H.,Shi, P.Y.,Bu, Z.,Huang, J.,Hu, Q.
Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro.
Acs Cent.Sci., 9:217-227, 2023

PubMed Abstract: The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment.

PubMed: 36844503
DOI: 10.1021/acscentsci.2c01359

実験手法

X-RAY DIFFRACTION (1.83 Å)