Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71 |
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| Authors: | Chen Zhao Liuyun Tang Haixia Ren Peng Li Ning Li Jianwei Huang Xueqin Chen Yi Guan Han You Shuhui Chen Jian Li Tianwei Lin |
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| Affiliation: | 1. 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;2. State Key Laboratory on Lead Compound Research, WuXi AppTech Co., Ltd., Shanghai, China;3. Xianmen Center for Disease Control and Prevention, Xiamen, China;4. Xiamen Hospital of Traditional Chinese Medicine, Xiamen, China;5. Fujian University for Traditional Chinese Medicine, Fuzhou, China;6. State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong, Hong Kong SAR, China |
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| 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 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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| Keywords: | enterovirus 71 3C proteinase cysteine protease hand, foot and mouth disease drug interaction drug design and development |
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