7DNC

Crystal structure of EV71 3C proteinase in complex with a novel inhibitor

これはPDB形式変換不可エントリーです。

7DNC の概要

• エントリーDOI: 10.2210/pdb7dnc/pdb
• 分子名称: 3C protease, ~{N}-[(2~{S})-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-3-phenyl-propan-2-yl]-1~{H}-indole-2-carboxamide (3 entities in total)
• 機能のキーワード: 3cpro, inhibitor, complex, hydrolase
• 由来する生物種: Human enterovirus 71 (EV71)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 20580.55

構造登録者

Xie, H.,Su, H.X.,Li, M.J.,Xu, Y.C. (登録日: 2020-12-09, 公開日: 2021-05-05, 最終更新日: 2024-12-18)

主引用文献

Dai, W.,Jochmans, D.,Xie, H.,Yang, H.,Li, J.,Su, H.,Chang, D.,Wang, J.,Peng, J.,Zhu, L.,Nian, Y.,Hilgenfeld, R.,Jiang, H.,Chen, K.,Zhang, L.,Xu, Y.,Neyts, J.,Liu, H.
Design, Synthesis, and Biological Evaluation of Peptidomimetic Aldehydes as Broad-Spectrum Inhibitors against Enterovirus and SARS-CoV-2.
J.Med.Chem., 65:2794-2808, 2022

PubMed Abstract: A novel series of peptidomimetic aldehydes was designed and synthesized to target 3C protease (3C) of enterovirus 71 (EV71). Most of the compounds exhibited high antiviral activity, and among them, compound demonstrated potent enzyme inhibitory activity and broad-spectrum antiviral activity on a panel of enteroviruses and rhinoviruses. The crystal structure of EV71 3C in complex with determined at a resolution of 1.2 Å revealed that covalently linked to the catalytic Cys147 with an aldehyde group. In addition, these compounds also exhibited good inhibitory activity against the 3CL and the replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially compound (IC = 0.034 μM, EC = 0.29 μM). According to our previous work, these compounds have no reasons for concern regarding acute toxicity. Compared with , compound also exhibited good pharmacokinetic properties and more potent anticoronavirus activity, making it an excellent lead for further development.

PubMed: 33872498
DOI: 10.1021/acs.jmedchem.0c02258

実験手法

X-RAY DIFFRACTION (1.17 Å)