Research on the resistance of hepatitis B virus to core protein allosteric modulators
10.11665/j.issn.1000-5048.2025040901
- VernacularTitle:乙型肝炎病毒对核心蛋白变构调节剂的耐药性研究
- Author:
Zechun YANG
1
;
Yuanyuan LIU
;
Minghui LIANG
;
Hewang WANG
;
Jie YANG
;
Peng ZHAN
;
Haiyong JIA
Author Information
1. 山东第二医科大学药学院, 潍坊 261053;青州市人民医院, 潍坊 262500;山东大学药学院, 济南 250012
- Publication Type:Journal Article 期刊文章
- Keywords:
hepatitis B virus;
core protein allosteric modulators;
drug resistance;
strategies to combat drug resistance
- From:
Journal of China Pharmaceutical University
2025;56(6):700-709
- CountryChina
- Language:Chinese
-
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.
