6M0K

The crystal structure of COVID-19 main protease in complex with an inhibitor 11b

6M0K の概要

• エントリーDOI: 10.2210/pdb6m0k/pdb
• 関連するBIRD辞書のPRD_ID: PRD_002349
• 分子名称: 3C-like proteinase, DIMETHYL SULFOXIDE, ~{N}-[(2~{S})-3-(3-fluorophenyl)-1-oxidanylidene-1-[[(2~{S})-1-oxidanylidene-3-[(3~{S})-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]propan-2-yl]-1~{H}-indole-2-carboxamide, ... (4 entities in total)
• 機能のキーワード: protease, 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: 34327.27

構造登録者

Zhang, B.,Zhao, Y.,Jin, Z.,Liu, X.,Yang, H.,Liu, H.,Rao, Z.,Jiang, H. (登録日: 2020-02-22, 公開日: 2020-04-29, 最終更新日: 2024-10-23)

主引用文献

Dai, W.,Zhang, B.,Jiang, X.M.,Su, H.,Li, J.,Zhao, Y.,Xie, X.,Jin, Z.,Peng, J.,Liu, F.,Li, C.,Li, Y.,Bai, F.,Wang, H.,Cheng, X.,Cen, X.,Hu, S.,Yang, X.,Wang, J.,Liu, X.,Xiao, G.,Jiang, H.,Rao, Z.,Zhang, L.K.,Xu, Y.,Yang, H.,Liu, H.
Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease.
Science, 368:1331-1335, 2020

PubMed Abstract: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is the etiological agent responsible for the global COVID-19 (coronavirus disease 2019) outbreak. The main protease of SARS-CoV-2, M, is a key enzyme that plays a pivotal role in mediating viral replication and transcription. We designed and synthesized two lead compounds ( and ) targeting M Both exhibited excellent inhibitory activity and potent anti-SARS-CoV-2 infection activity. The x-ray crystal structures of SARS-CoV-2 M in complex with or , both determined at a resolution of 1.5 angstroms, showed that the aldehyde groups of and are covalently bound to cysteine 145 of M Both compounds showed good pharmacokinetic properties in vivo, and also exhibited low toxicity, which suggests that these compounds are promising drug candidates.

PubMed: 32321856
DOI: 10.1126/science.abb4489

実験手法

X-RAY DIFFRACTION (1.504 Å)