7E19

Crystal structure of SAR-CoV-2 3CL protease complex with inhibitor SH-5

7E19 の概要

• エントリーDOI: 10.2210/pdb7e19/pdb
• 分子名称: 3C-like proteinase, (phenylmethyl) N-[(2S)-1-[[(2S)-1-[[(2S)-1-(1,3-benzothiazol-2-yl)-1-oxidanylidene-3-[(3S)-2-oxidanylidenepyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxidanylidene-pentan-2-yl]amino]-3-methyl-1-oxidanylidene-butan-2-yl]carbamate (3 entities in total)
• 機能のキーワード: sars-cov-2 3cl protease, hydrolase
• 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: 34461.32

構造登録者

Senda, M.,Konno, S.,Hayashi, Y.,Senda, T. (登録日: 2021-02-01, 公開日: 2021-06-23, 最終更新日: 2023-11-29)

主引用文献

Konno, S.,Kobayashi, K.,Senda, M.,Funai, Y.,Seki, Y.,Tamai, I.,Schakel, L.,Sakata, K.,Pillaiyar, T.,Taguchi, A.,Taniguchi, A.,Gutschow, M.,Muller, C.E.,Takeuchi, K.,Hirohama, M.,Kawaguchi, A.,Kojima, M.,Senda, T.,Shirasaka, Y.,Kamitani, W.,Hayashi, Y.
3CL Protease Inhibitors with an Electrophilic Arylketone Moiety as Anti-SARS-CoV-2 Agents.
J.Med.Chem., 65:2926-2939, 2022

PubMed Abstract: The novel coronavirus, SARS-CoV-2, has been identified as the causative agent for the current coronavirus disease (COVID-19) pandemic. 3CL protease (3CL) plays a pivotal role in the processing of viral polyproteins. We report peptidomimetic compounds with a unique benzothiazolyl ketone as a warhead group, which display potent activity against SARS-CoV-2 3CL. The most potent inhibitor YH-53 can strongly block the SARS-CoV-2 replication. X-ray structural analysis revealed that YH-53 establishes multiple hydrogen bond interactions with backbone amino acids and a covalent bond with the active site of 3CL. Further results from computational and experimental studies, including an absorption, distribution, metabolism, and excretion profile, pharmacokinetics, and metabolic analysis of YH-53 suggest that it has a high potential as a lead candidate to compete with COVID-19.

PubMed: 34313428
DOI: 10.1021/acs.jmedchem.1c00665

実験手法

X-RAY DIFFRACTION (2.15 Å)