title: Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71.
abstract: Enterovirus 71 (EV71) is the causative agent of hand, foot and mouth disease and can spread its infections to the central nervous and other systems with severe consequences. The replication of EV71 depends on its 3C proteinase (3Cpro), a significant drug target. By X-ray crystallography and functional assays, the interactions between inhibitors and EV71 3Cprowere evaluated. It was shown that improved interactions at S4 for the substrate binding could significantly enhance the potency. A new series of potent inhibitors with high ligand efficiency was generated for developing antivirals to treat and control the EV71-associated diseases. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Lanjun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Guolong
authors.initials: G
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Qixu
authors.initials: Q
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Liuyun
authors.initials: L
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Ren
authors.affiliation: State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: Xianmen Center for Disease Control and Prevention, Shen-guang Road 681-685, Xiamen, 361021, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361001, China.|Fujian University for Traditional Chinese Medicine, Fuzhou, 350004, China.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China.
authors.forename: Han
authors.initials: H
authors.lastname: You
authors.affiliation: State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131, China.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131, China. jian_li@wuxiapptec.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, State-Province Joint Engineering Laboratory of Targeted Drugs from Natural Products, School of Life Sciences, Xiamen University, Xiamen, Fujian, China. twlin@xmu.edu.cn.
authors.forename: Tianwei
authors.initials: T
authors.lastname: Lin
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D003546:Cysteine Endopeptidases / Q000737:chemistry; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D029821:Enterovirus A, Human / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014764:Viral Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000998:Antiviral Agents; D015853:Cysteine Proteinase Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases
keywords: 3C proteinase; cysteine protease; drug design and development; drug interaction; enterovirus 71; hand, foot and mouth disease