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Bioorg Med Chem Lett. 2018 Aug 1;28(14):2533-2538. doi: 10.1016/j.bmcl.2018.05.046. Epub 2018 May 29.

Identification of quinone analogues as potential inhibitors of picornavirus 3C protease in vitro.

Author information

1
Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: e-hyeya@hanmail.net.
2
Drug Information Platform Center, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: leejy@krict.re.kr.
3
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womens University, Seoul 03760, Republic of Korea. Electronic address: gloria1992@hanmail.net.
4
College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womens University, Seoul 03760, Republic of Korea. Electronic address: ckryu@ewha.ac.kr.
5
Green Carbon Catalysis Group, Carbon Resources Institute, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: kilee@krict.re.kr.
6
Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Republic of Korea. Electronic address: mkim@krict.re.kr.
7
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea. Electronic address: ckyolee@krict.re.kr.
8
Virus Research Group, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea; Department of Medicinal Chemistry and Pharmacology, University of Science and Technology, Daejeon 34114, Republic of Korea. Electronic address: yygo@krict.re.kr.

Abstract

Picornaviruses are non-enveloped viruses that represent a large family of positive-sense single-stranded RNA viruses including a number of causative agents of many human and animal diseases such as coxsackievirus B3 (CVB3) and rhinoviruses (HRV). In this study, we performed a high-throughput screening of a compound library composed of ∼6000 small molecules in search of potential picornavirus 3C protease (3Cpro) inhibitors. As results, we identified quinone analogues that effectively inhibited both CVB3 3Cpro and HRV 3Cpro with IC50 values in low micromolar range. Together with predicted binding modes of these compounds to the active site of the viral protease, it is implied that structural features of these non-peptidic inhibitors may act as useful scaffold for further anti-picornavirus drug design and development.

KEYWORDS:

3C protease inhibitors; Antivirals; Coxsackievirus B3; Picornavirus

PMID:
29866517
DOI:
10.1016/j.bmcl.2018.05.046
[Indexed for MEDLINE]

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