2. Academic Validation
  3. Discovery of aminothiazole derivatives as novel human enterovirus A71 capsid protein inhibitors

Discovery of aminothiazole derivatives as novel human enterovirus A71 capsid protein inhibitors

  • Bioorg Chem. 2022 May;122:105683. doi: 10.1016/j.bioorg.2022.105683.
Zhichao Xu 1,  Qi Tang 2,  Ting Xu 1,  Yang Cai 3,  Ping Lei 3,  Yinuo Chen 3,  Wenting Zou 1,  Chune Dong 1,  Ke Lan 4,  Shuwen Wu 5,  Hai-Bing Zhou 6
Affiliations

Affiliations

  • 1 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.
  • 2 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; Department of Microbiology, The Key Laboratory of Microbiology and Parasitology of Anhui Province, The Key Laboratory of Zoonoses of High Institutions in Anhui, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
  • 3 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
  • 4 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China; Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China. Electronic address: klan@whu.edu.cn.
  • 5 State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China. Electronic address: shuwenwu@whu.edu.cn.
  • 6 Hubei Provincial Key Laboratory of Developmentally Originated Disease, Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China; Medical Research Institute, Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, China. Electronic address: zhouhb@whu.edu.cn.
PMID: 35278779 DOI: 10.1016/j.bioorg.2022.105683
Abstract

Enterovirus A71 (EV-A71), one of the major pathogens that causes hand, foot and mouth disease (HFMD), has seriously threatened the health and safety of young children. In this study, aminothiazole derivatives were synthesized and screened against EV-A71 in Rhabdomyosarcoma (RD) cells. The best compound (12s), with a biphenyl group, showed activity against EV-A71 (EC50: 0.27 μM) but also against a series of different human enteroviruses without significant cytotoxicity (CC50 > 56.2 μM). Mechanistic studies including time-of-drug-addition assays, viral entry assays and microscale thermophoresis (MST) experiments, showed that 12s binds to EV-A71 capsid and blocks the binding between the viral protein VP1 and the relevant human scavenger receptor class B member 2 (hSCARB2).

Keywords

Aminothiazole analogs; Capsid protein; EV-A71; HSCARB2; MST assay; Structure-activity relationship.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z