Yang Li, Liu Feifei, Tong Xiankun, Hoffmann Daniel, Zuo Jianping, Lu Mengji
Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica , Chinese Academy of Sciences , Zhangjiang Hi-Tech Park, 555 Zuchongzhi Road , Shanghai 201203 , China.
University of Chinese Academy of Sciences , No. 19A Yuquan Road , Beijing 100049 , China.
ACS Infect Dis. 2019 May 10;5(5):713-724. doi: 10.1021/acsinfecdis.8b00337. Epub 2019 Mar 29.
On the basis of the recent advance of basic research on molecular biology of hepatitis B virus (HBV) infection, novel antiviral drugs targeting various steps of the HBV life cycle have been developed in recent years. HBV nucleocapsid assembly is now recognized as a hot target for anti-HBV drug development. Structural and functional analysis of HBV nucleocapsid allowed rational design and improvement of small molecules with the ability to interact with the components of HBV nucleocapsid and modulate the viral nucleocapsid assembly process. Prototypes of small molecule modulators targeting HBV nucleocapsid assembly are being preclinically tested or have moved forward in clinical trials, with promising results. This Review summarizes the recent advances in the approach to develop antiviral drugs based on the modulation of HBV nucleocapsid assembly. The antiviral mechanisms of small molecule modulators beyond the capsid formation and the potential implications will be discussed.
基于近年来乙型肝炎病毒（HBV）感染分子生物学基础研究的进展，近年来已开发出针对HBV生命周期各个步骤的新型抗病毒药物。HBV核衣壳组装目前被认为是抗HBV药物开发的热点靶点。对HBV核衣壳的结构和功能分析使得能够合理设计和改进具有与HBV核衣壳成分相互作用并调节病毒核衣壳组装过程能力的小分子。靶向HBV核衣壳组装的小分子调节剂原型正在进行临床前测试，或已进入临床试验阶段，并取得了令人鼓舞的结果。本综述总结了基于调节HBV核衣壳组装来开发抗病毒药物方法的最新进展。还将讨论小分子调节剂在衣壳形成之外的抗病毒机制及其潜在影响。
