國家衛生研究院 NHRI:Item 3990099045/12808

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Title:	Discovery of M protease inhibitors encoded by SARS-CoV-2
Authors:	Hung, HC;Ke, YY;Huang, SY;Huang, PN;Kung, YA;Chang, TY;Yen, KJ;Peng, TT;Chang, SE;Huang, CT;Tsai, YR;Wu, SH;Lee, SJ;Lin, JH;Liu, BS;Sung, WC;Shih, SR;Chen, CT;Hsu, JT
Contributors:	Institute of Biotechnology and Pharmaceutical Research;National Institute of Infectious Diseases and Vaccinology
Abstract:	The COVID-19 pandemic caused by SARS-CoV-2 is a health threat worldwide. Viral main protease (M(pro), also called 3C-like protease, 3CL(pro)) is a therapeutic target for drug discovery. Herein, we report that GC376, a broad-spectrum inhibitor targeting M(pro) in the picornavirus-like supercluster, is potent inhibitor for the M(pro) encoded by SARS-CoV-2 with half-maximum inhibitory concentration (IC(50)) of 26.4±1.1 nM. In this study, we also show that GC376 inhibits SARS-CoV-2 replication with a half-maximum effective concentration (EC(50)) of 0.91±0.03 μM. Only a small portion of SARS-CoV-2-M(pro) was covalently modified in the excess of GC376 as evaluated by mass spectrometry analysis; indicating that improved inhibitors are needed. Subsequently, molecular docking analysis revealing the recognition and binding groups of GC376 within the active site of SARS-CoV-2 M(pro) provides important new information for the optimization of GC376. Given that sufficient safety and efficacy data are available for GC376 as an investigational veterinary drug, expedited development of GC376, or its optimized analogues, for treatment of SARS-CoV-2 infection in human is recommended.
Date:	2020-08-20
Relation:	Antimicrobial Agents and Chemotherapy. 2020 Aug 20;64(9):e00872-20.
Link to:	http://dx.doi.org/10.1128/aac.00872-20
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0066-4804&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000566461500005
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85089786845
Appears in Collections:	[John Tsu-An Hsu] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Shiow-Ju Lee] Periodical Articles [Wang-Chou Sung] Periodical Articles

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