Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71
Lanjun Zhang
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
These authors contribute equally to this work.Search for more papers by this authorGuolong Huang
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
These authors contribute equally to this work.Search for more papers by this authorQixu Cai
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
These authors contribute equally to this work.Search for more papers by this authorChen Zhao
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
Search for more papers by this authorLiuyun Tang
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
Search for more papers by this authorHaixia Ren
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
Search for more papers by this authorPeng Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorNing Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorJianwei Huang
Xianmen Center for Disease Control and Prevention, Shen-guang Road 681-685, Xiamen, 361021 China
Search for more papers by this authorXueqin Chen
Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361001 China
Fujian University for Traditional Chinese Medicine, Fuzhou, 350004 China
Search for more papers by this authorYi Guan
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China
Search for more papers by this authorHan You
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
Search for more papers by this authorShuhui Chen
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorCorresponding Author
Jian Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Correspondence to: Tianwei Lin, 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,Xiang'an South Road, Xiang'an District, Xiamen 361102, China.
E-mail: [email protected]
Correspondence to: Jian Li, State Key Laboratory on Lead Compound Research, WuXi AppTech Co. 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Tianwei Lin
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
Correspondence to: Tianwei Lin, 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,Xiang'an South Road, Xiang'an District, Xiamen 361102, China.
E-mail: [email protected]
Correspondence to: Jian Li, State Key Laboratory on Lead Compound Research, WuXi AppTech Co. 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
E-mail: [email protected]
Search for more papers by this authorLanjun Zhang
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
These authors contribute equally to this work.Search for more papers by this authorGuolong Huang
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
These authors contribute equally to this work.Search for more papers by this authorQixu Cai
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
These authors contribute equally to this work.Search for more papers by this authorChen Zhao
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
Search for more papers by this authorLiuyun Tang
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
Search for more papers by this authorHaixia Ren
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
Search for more papers by this authorPeng Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorNing Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorJianwei Huang
Xianmen Center for Disease Control and Prevention, Shen-guang Road 681-685, Xiamen, 361021 China
Search for more papers by this authorXueqin Chen
Xiamen Hospital of Traditional Chinese Medicine, Xiamen, 361001 China
Fujian University for Traditional Chinese Medicine, Fuzhou, 350004 China
Search for more papers by this authorYi Guan
State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China
Search for more papers by this authorHan You
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
Search for more papers by this authorShuhui Chen
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Search for more papers by this authorCorresponding Author
Jian Li
State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, 200131 China
Correspondence to: Tianwei Lin, 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,Xiang'an South Road, Xiang'an District, Xiamen 361102, China.
E-mail: [email protected]
Correspondence to: Jian Li, State Key Laboratory on Lead Compound Research, WuXi AppTech Co. 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
E-mail: [email protected]
Search for more papers by this authorCorresponding Author
Tianwei Lin
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
Correspondence to: Tianwei Lin, 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,Xiang'an South Road, Xiang'an District, Xiamen 361102, China.
E-mail: [email protected]
Correspondence to: Jian Li, State Key Laboratory on Lead Compound Research, WuXi AppTech Co. 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
E-mail: [email protected]
Search for more papers by this authorAbstract
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 3Cpro were 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.
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