6WTJ

Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication

6WTJ の概要

• エントリーDOI: 10.2210/pdb6wtj/pdb
• 分子名称: 3C-like proteinase, (1S,2S)-2-({N-[(benzyloxy)carbonyl]-L-leucyl}amino)-1-hydroxy-3-[(3S)-2-oxopyrrolidin-3-yl]propane-1-sulfonic acid (3 entities in total)
• 機能のキーワード: covid-19, sars-cov-2, 3clpro, coronavirus, main protease, kinetics, sars, viral protein, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 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: 34311.10

構造登録者

Khan, M.B.,Arutyunova, E.,Young, H.S.,Lemieux, M.J. (登録日: 2020-05-02, 公開日: 2020-05-20, 最終更新日: 2024-11-06)

主引用文献

Vuong, W.,Khan, M.B.,Fischer, C.,Arutyunova, E.,Lamer, T.,Shields, J.,Saffran, H.A.,McKay, R.T.,van Belkum, M.J.,Joyce, M.A.,Young, H.S.,Tyrrell, D.L.,Vederas, J.C.,Lemieux, M.J.
Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication.
Nat Commun, 11:4282-4282, 2020

PubMed Abstract: The main protease, M (or 3CL) in SARS-CoV-2 is a viable drug target because of its essential role in the cleavage of the virus polypeptide. Feline infectious peritonitis, a fatal coronavirus infection in cats, was successfully treated previously with a prodrug GC376, a dipeptide-based protease inhibitor. Here, we show the prodrug and its parent GC373, are effective inhibitors of the M from both SARS-CoV and SARS-CoV-2 with IC values in the nanomolar range. Crystal structures of SARS-CoV-2 M with these inhibitors have a covalent modification of the nucleophilic Cys145. NMR analysis reveals that inhibition proceeds via reversible formation of a hemithioacetal. GC373 and GC376 are potent inhibitors of SARS-CoV-2 replication in cell culture. They are strong drug candidates for the treatment of human coronavirus infections because they have already been successful in animals. The work here lays the framework for their use in human trials for the treatment of COVID-19.

PubMed: 32855413
DOI: 10.1038/s41467-020-18096-2

実験手法

X-RAY DIFFRACTION (1.9 Å)