6XHM

Covalent complex of SARS-CoV-2 main protease with N-[(2S)-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide

6XHM の概要

• エントリーDOI: 10.2210/pdb6xhm/pdb
• 分子名称: 3C-like proteinase, N-[(2S)-1-({(2S,3S)-3,4-dihydroxy-1-[(3S)-2-oxopyrrolidin-3-yl]butan-2-yl}amino)-4-methyl-1-oxopentan-2-yl]-4-methoxy-1H-indole-2-carboxamide, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: coronavirus protease inhibitor complex, 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: 68662.26

構造登録者

Gajiwala, K.S.,Ferre, R.A.,Ryan, K.,Stewart, A.E. (登録日: 2020-06-19, 公開日: 2020-07-08, 最終更新日: 2024-10-16)

主引用文献

Hoffman, R.L.,Kania, R.S.,Brothers, M.A.,Davies, J.F.,Ferre, R.A.,Gajiwala, K.S.,He, M.,Hogan, R.J.,Kozminski, K.,Li, L.Y.,Lockner, J.W.,Lou, J.,Marra, M.T.,Mitchell Jr., L.J.,Murray, B.W.,Nieman, J.A.,Noell, S.,Planken, S.P.,Rowe, T.,Ryan, K.,Smith 3rd, G.J.,Solowiej, J.E.,Steppan, C.M.,Taggart, B.
Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19.
J.Med.Chem., 63:12725-12747, 2020

PubMed Abstract: The novel coronavirus disease COVID-19 that emerged in 2019 is caused by the virus SARS CoV-2 and named for its close genetic similarity to SARS CoV-1 that caused severe acute respiratory syndrome (SARS) in 2002. Both SARS coronavirus genomes encode two overlapping large polyproteins, which are cleaved at specific sites by a 3C-like cysteine protease (3CL) in a post-translational processing step that is critical for coronavirus replication. The 3CL sequences for CoV-1 and CoV-2 viruses are 100% identical in the catalytic domain that carries out protein cleavage. A research effort that focused on the discovery of reversible and irreversible ketone-based inhibitors of SARS CoV-1 3CL employing ligand-protease structures solved by X-ray crystallography led to the identification of and . Preclinical experiments reveal () as a potent inhibitor of CoV-2 3CL with suitable pharmaceutical properties to warrant further development as an intravenous treatment for COVID-19.

PubMed: 33054210
DOI: 10.1021/acs.jmedchem.0c01063

実験手法

X-RAY DIFFRACTION (1.406 Å)