Discovery of Potent EV71 Capsid Inhibitors for Treatment
of HFMD

Li, Peng; Yu, Jun; Hao, Fei; He, Haiying; Shi, Xuyang; Hu, Jiao; Wang, Li; Du, Chunyan; Zhang, Xiao; Sun, Ya; Lin, Fusen; Gu, Zhengxian; Xu, Deming; Chen, Xinsheng; Shen, Liang; Hu, Guoping; Li, Jian; Chen, Shuhui; Xiao, Wei; Wang, Zhenzhong; Guo, Qingming; Chang, Xiujuan; Tian, Xuyang; Lin, Tianwei

doi:10.1021/acsmedchemlett.7b00188.s001

ml7b00188_si_001.pdf (682.36 kB)

Discovery of Potent EV71 Capsid Inhibitors for Treatment of HFMD

journal contribution

posted on 2017-07-10, 00:00 authored by Peng Li, Jun Yu, Fei Hao, Haiying He, Xuyang Shi, Jiao Hu, Li Wang, Chunyan Du, Xiao Zhang, Ya Sun, Fusen Lin, Zhengxian Gu, Deming Xu, Xinsheng Chen, Liang Shen, Guoping Hu, Jian Li, Shuhui Chen, Wei Xiao, Zhenzhong Wang, Qingming Guo, Xiujuan Chang, Xuyang Tian, Tianwei Lin

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which can spread its infections to the central nervous and other systems with severe consequences. The viral caspid protein VP1 is a well-known target for antiviral efficacy because its occupancy by suitable compounds could stabilize the virus capsid, thus preventing uncoating of virus for RNA release. In this Letter, design, synthesis, and biological evaluation of novel anti-EV71 agents (aminopyridyl 1,2,5-thiadiazolidine 1,1-dioxides) are described. One of the most promising compounds (14) showed excellent antiviral activity against EV71 (EC₅₀ = 4 nM) and exhibited excellent in vivo efficacy in the EV71 infected mouse model.