乙型肝炎病毒核心蛋白变构调节剂的作用机理及临床研发和应用前景  

Mechanism of action,clinical research and development,and application prospect of hepatitis B virus core protein allosteric modulators

作　　者：刘慧[1,2] 鲁凤民 郭巨涛[2] LIU Hui;LU Fengmin;GUO Jutao(Department of Microbiology and Infectious Disease Center,School of Basic Medical Sciences,Peking University Health Science Center,Beijing 100191,China;Baruch S.Blumberg Institute,Doylestown,Pennsylvania 18902,USA)

机构地区：[1]北京大学基础医学院病原生物学系暨感染病中心,北京100191 [2]巴鲁克布隆伯格研究所,美国宾夕法尼亚州18902

出　　处：《临床肝胆病杂志》2022年第8期1726-1732,共7页Journal of Clinical Hepatology

摘　　要：HBV感染是导致慢性肝炎的主要致病因素,若不及时、有效地规范治疗,将有进一步发展为肝硬化、肝细胞癌等终末期肝病的风险。临床现有的两类抗病毒药物皆无法彻底抑制病毒复制和清除病毒转录模板,即感染肝细胞内长期存在的共价闭合环状DNA(cccDNA),因而,慢性乙型肝炎患者需长期甚至终身服药。因此,研发新型抗HBV药物显得尤为重要。核心蛋白变构调节剂(CpAM)是一类新型抗HBV药物,其干扰HBV核衣壳装配过程,并对成熟核衣壳解聚、cccDNA形成和HBeAg的产生及分泌发挥抑制作用。因其广泛作用于病毒复制的多个环节,具备较大的应用潜力。本文主要阐述CpAM靶蛋白-核心蛋白的功能、CpAM分类、作用靶点及抗HBV机理、CpAM临床试验现状及进一步研发和应用前景。Hepatitis B virus(HBV)infection is the main pathogenic factor for chronic hepatitis,and if it is not treated timely and effective-ly,it may have the risk of developing into end-stage liver diseases such as liver cirrhosis and hepatocellular carcinoma.Neither of the two types of antiviral drugs currently used in clinical practice can completely inhibit viral replication or eliminate viral transcriptional template,which means that covalently closed circular DNA(cccDNA)exists in infected liver cells for a long time,and thus patients with chronic hep-atitis B require long-term or even lifelong medication.Therefore,it is of great importance to develop novel anti-HBV drugs.Core protein allosteric modulators(CpAM)are a type of novel anti-HBV drugs and can interfere with HBV nucleocapsid assembly and inhibit the depo-lymerization of mature nucleocapsid,the formation of cccDNA,and the biogenesis and secretion of HBeAg.CpAM have a great potential in clinical application since they act on various links of viral replication.This article reviews the function of CpAM target protein-core protein,the classification,action targets,and anti-HBV mechanism of CpAM,and the current research status,further development,and applica-tion prospect of CpAM.

关 键 词：乙型肝炎病毒 核心蛋白变构调节剂 临床试验 

分 类 号：R978.7[医药卫生—药品]