中国药科大学学报2025，Vol.56Issue(6)：700-709,10.DOI:10.11665/j.issn.1000-5048.2025040901
乙型肝炎病毒对核心蛋白变构调节剂的耐药性研究
Research on the resistance of hepatitis B virus to core protein allosteric modulators
摘要
Abstract
Hepatitis B virus(HBV)infection represents a significant global health challenge.Current therapeutic options,such as interferon and nucleoside analogues(NAs),are limited by issues including long-term medication toxicity,the virus's propensity to develop drug resistance,and the inability to eradicate covalently closed circular DNA(cccDNA).Core protein allosteric modulators(CpAMs),as an emerging class of anti-HBV drugs,target HBcAg to interfere with capsid assembly.This not only blocks viral nucleocapsid formation and inhibits viral replication but also indirectly destabilizes the cccDNA pool,while exhibiting a relatively high genetic barrier to resistance.This article systematically evaluates HBV drug resistance to CpAMs and proposes anti-resistance strategies,including the combination of nucleoside analogues with CpAMs,enhancing protein-drug interactions,targeting HBcAg degradation,designing multi-target inhibitors,and employing combination therapy.Looking ahead,the integration of structural biology,computational chemistry,and immunotherapy will offer innovative approaches for developing novel,highly effective,and low-resistance inhibitors,thereby advancing the functional cure of hepatitis B.关键词
乙肝病毒/核心蛋白变构调节剂/耐药性/抗耐药策略Key words
hepatitis B virus/core protein allosteric modulators/drug resistance/strategies to combat drug resistance分类
医药卫生引用本文复制引用
杨泽春,刘媛媛,梁明辉,王鹤望,杨洁,展鹏,贾海永..乙型肝炎病毒对核心蛋白变构调节剂的耐药性研究[J].中国药科大学学报,2025,56(6):700-709,10.基金项目
国家重点研发计划项目(No.2023YFC2606500) （No.2023YFC2606500）
国家自然科学基金项目(No.81903468) （No.81903468）
山东第二医科大学大学生创新创业训练计划项目(X2024121) （X2024121）
潍坊市科技发展计划项目(No.2023YX038) This study was supported by the National Key Research and Development Program of China(No.2023YFC2606500),the National Natural Science Foundation of China(No.81903468),the Undergraduates Innovation and Entrepreneurship Training Program for Shandong Second Medical University(X2024121),and the Science and Technology Development Project of Weifang City(No.2023YX038) （No.2023YX038）
