HBV衣壳组装调节剂的临床研究新进展  

Recent progress of clinical research on modulators of HBV capsid assembly

作　　者：徐慧 唐凯 周加慧 刘新泳[1] 展鹏[1] XU Hui;TANG Kai;ZHOU Jiahui;LIU Xinyong;ZHAN Peng(Department of Medicinal Chemistry,School of Pharmaceutical Sciences,Shandong University,Ji'nan 250012,China)

机构地区：[1]山东大学药学院药物化学研究所,山东济南250012

出　　处：《中国药物化学杂志》2025年第1期59-76,共18页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金面上项目(82173677);山东省杰出青年基金项目(ZR2020JQ31);山东省重大科技创新工程项目(2019JZZY021011)。

摘　　要：乙型肝炎是由乙型肝炎病毒(hepatitis B virus,HBV)所致的病毒性肝炎,具有患病率高和难治愈的特点。近年来,HBV衣壳组装调节剂通过加速核衣壳组装或诱导核心蛋白的异构化来调节HBV衣壳的组装过程,从而导致非感染性病毒颗粒(空衣壳)的产生,进而抑制HBV复制。该类调节剂是当前抗HBV药物研究的重要方向。HBV衣壳组装调节剂主要分为两类,分别是以Bay 41-409和GLS4为代表的Ⅰ类调节剂及以NVR 3-778、AT-130和JNJ-6379为代表的Ⅱ类调节剂,这两类均有多个候选药物进入临床试验。本文作者全面阐述了HBV衣壳组装调节剂候选药物的临床研究现状,并探讨了靶向HBV药物所面临的机遇、挑战及前景,旨在为抗HBV药物研发提供参考。Hepatitis B is a viral liver inflammation caused by the hepatitis B virus(HBV),characterized by a high incidence rate,and challenges in achieving complete remission.In recent years,HBV capsid assembly modulators(CAMs)have emerged as crucial agents in the treatment of hepatitis B virus(HBV).These CAMs regulate the assembly process of HBV capsids by either expediting their formation or inducing conformational changes in the core protein.Consequently,this leads to the generation of non-infectious viral particles(empty capsids),effectively impeding HBV replication.The development of such regulators represents a significant direction in ongoing research on anti-HBV drugs.CAMs are mainly divided into two categories,namely classⅠmodulators represented by Bay 41-409 and GLS4,and classⅡmodulators represented by NVR 3-778,AT-130,and JNJ-6379.Multiple candidate drugs have been approved for clinical trials.This review comprehensively describes the clinical research status of CAMs candidate drugs,and discusses the opportunities,challenges and prospects of targeted CAMs drugs in the research field,aiming to provide a reference for the research and development of anti-HBV drugs.

关 键 词：HBV 衣壳 衣壳组装调节剂 临床试验 抗病毒 

分 类 号：R914[医药卫生—药物化学]