9OCK

Co-Structure of Main Protease of SARS-CoV-2 with Compound 1

これはPDB形式変換不可エントリーです。

9OCK の概要

• エントリーDOI: 10.2210/pdb9ock/pdb
• 分子名称: 3C-like proteinase nsp5, 2-fluoro-N-(isoquinolin-4-yl)-5-(trifluoromethyl)benzamide, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: hydrolase
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34182.80

構造登録者

Knapp, M.S.,Ornelas, E. (登録日: 2025-04-24, 公開日: 2026-02-18, 最終更新日: 2026-03-11)

主引用文献

Papillon, J.P.N.,Yuan, J.,Hesse, M.J.,Zhang, L.,Robinson, R.I.,Ware, N.F.,Hornak, V.,Karki, R.G.,Kirrane, T.,Garland, K.,Joseph, S.,Moquin, S.A.,Lakshminarayana, S.B.,Tandeske, L.,Dovala, D.,Knapp, M.,Ornelas, E.,Fuller, D.,Ho, P.I.,Xie, X.,Vulic, K.,Skolnik, S.M.,Gao, J.,Zambrowski, M.,Spiess, M.,Duca, J.S.,Busby, S.A.,Schirle, M.,Robinson, M.,Shi, P.Y.,Moser, H.E.,Sarko, C.,Bradner, J.E.,Diagana, T.T.,Tallarico, J.A.
Discovery of EGT710, an Oral Nonpeptidomimetic Reversible Covalent SARS-CoV-2 Main Protease Inhibitor.
J.Med.Chem., 69:3868-3886, 2026

PubMed Abstract: The coronavirus main protease (3CL, M, nsp5) is a highly conserved cysteine protease unique to the Coronaviridae family, including SARS-CoV-2, and is a validated target for the treatment of COVID-19. Our efforts focused on the identification of a nonpeptidomimetic M inhibitor, due to the potential for superior pharmacological properties. Herein, we report our efforts leveraging virtual screening and X-ray crystallography that enabled a structure-based drug design approach, leading to the discovery of series of quinazoline-2,4(1,3)-dione and oxoimidazolidine-4-carbonitrile compounds with potent inhibition of SARS-CoV-2 M as well as other coronaviruses main proteases. Extensive lead optimization focusing on pharmacokinetic properties, developability, and breadth of activity across coronaviruses, led to the identification of . demonstrates excellent potency against SARS-CoV-2 infection in a primary differentiated normal human bronchial epithelial (dNHBE) cellular assay, as well as a favorable pharmacology profile that supported advancement into preclinical and clinical studies.

PubMed: 41663073
DOI: 10.1021/acs.jmedchem.5c02360

実験手法

X-RAY DIFFRACTION (1.6 Å)