9KGR

Discovery of an orally bioavailable reversible covalent SARS-CoV-2 Mpro inhibitor with pan-coronavirus activity

これはPDB形式変換不可エントリーです。

9KGR の概要

• エントリーDOI: 10.2210/pdb9kgr/pdb
• 分子名称: 3C-like proteinase nsp5, (S)-2-((R)-2-cyclopentyl-2-pivalamidoacetamido)-N-((2S,3R)-4-(cyclopropylamino)-3-hydroxy-4-oxo-1-((S)-2-oxopiperidin-3-yl)butan-2-yl)pentanamide, cyclopropylcarbamic acid, ... (4 entities in total)
• 機能のキーワード: protease, cov2, hydrolase, hydrolase-inhibitor complex, hydrolase/inhibitor
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 69665.46

構造登録者

Baburajendran, N. (登録日: 2024-11-08, 公開日: 2025-08-20, 最終更新日: 2025-09-10)

主引用文献

Tan, Q.W.,Vankadara, S.,Fong, J.Y.,See, Y.Y.,Baburajendran, N.,Ng, P.S.,Xu, W.,Yeo, Y.K.,Wang, W.,Low, C.H.,Tan, L.H.,Ju Tay, E.G.,Wong, Y.X.,Huang, C.,Sim, S.,Ang, S.H.,Min Toh, H.H.,Mohammad, J.,Wang, G.,Liu, B.,Tan, S.T.,Kwek, P.Z.,Dawson, M.D.,Oh, Q.Y.,Koh, X.,Joy, J.,Lee, M.A.,Stunkel, W.,Pendharkar, V.,Hentze, H.,Lim, S.P.,Ethirajulu, K.,Brian Chia, C.S.,Cherian, J.
Discovery of an Orally Bioavailable Reversible Covalent SARS-CoV-2 M pro Inhibitor with Pan-Coronavirus Activity.
J.Med.Chem., 68:17087-17102, 2025

PubMed Abstract: Resulting in several million deaths globally, the COVID-19 pandemic has highlighted the criticality of antiviral drugs during a viral pandemic. Herein, we describe our efforts toward targeting SARS-CoV-2 M, a key viral protease, which led to the discovery of compound , a reversible covalent inhibitor with potent antiviral activity against several clinical variants of SARS-CoV-2. Compound demonstrated dose-dependent efficacy in a mouse-adapted SARS-CoV-2 infection model, with favorable pharmacokinetic profiles in mice, rats, dogs, and monkeys.

PubMed: 40773370
DOI: 10.1021/acs.jmedchem.5c00581

実験手法

X-RAY DIFFRACTION (1.47 Å)