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Small molecule NS5B RdRp non-nucleoside inhibitors for the treatment of HCV infection: A medicinal chemistry perspective

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机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [3]Department of Pharmacy, Chengdu Fifth People’s Hospital, Chengdu, Sichuan, 611130, China [4]Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, 38163, Tennessee, United States [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [6]Tianfu Jincheng Laboratory, Chengdu, 610041, Sichuan, China

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Hepatitis C virus (HCV) infection has become a global health problem with enormous risks. Nonstructural protein 5B (NS5B) RNA-dependent RNA polymerase (RdRp) is a component of HCV, which can promote the formation of the viral RNA replication complex and is also an essential part of the replication complex itself. It plays a vital role in the synthesis of the positive and negative strands of HCV RNA. Therefore, the development of small-molecule inhibitors targeting NS5B RdRp is of great value for treating HCV infection-related diseases. Compared with NS5B RdRp nucleoside inhibitors, non-nucleoside inhibitors have more flexible structures, simpler mechanisms of action, and more predictable efficacy and safety of drugs in humans. Technological advances over the past decade have led to remarkable achievements in developing NS5B RdRp inhibitors. This review will summarize the non-nucleoside inhibitors targeting NS5B RdRp developed in the past decade and describe their structure optimization process and structure-activity relationship.Copyright © 2022 Elsevier Masson SAS. All rights reserved.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区药物化学

最新[2025]版：

大类 | 2 区医学

小类 | 1 区药物化学

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第一作者机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

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通讯机构： [1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [2]State Key Laboratory of Biotherapy and Cancer Center, Department of Respiratory and Critical Care Medicine, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [5]Precision Medicine Key Laboratory of Sichuan Province & Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China [6]Tianfu Jincheng Laboratory, Chengdu, 610041, Sichuan, China [*1]Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

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