The premise of capsid assembly modulators towards eliminating HBV persistence

被引:8
作者
Bassit, Leda [1 ,2 ]
Amblard, Franck [1 ,2 ]
Patel, Dharmeshkumar [1 ,2 ]
Biteau, Nicolas [1 ,2 ]
Chen, Zhe [1 ,2 ]
Kasthuri, Mahesh [1 ,2 ]
Zhou, Shaoman [1 ,2 ]
Schinazi, Raymond F. [1 ,2 ,3 ,4 ]
机构
[1] Emory Univ, Ctr ViroSci & Cure, Dept Pediat, Lab Biochem Pharmacol,Sch Med, Atlanta, GA USA
[2] Childrens Healthcare Atlanta, Atlanta, GA USA
[3] Emory Univ, Ctr ViroSci & Cure, Dept Pediat, Lab Biochem Pharmacol,Sch Med, 1760 Haygood Dr, Atlanta, GA 30322 USA
[4] Childrens Healthcare Atlanta, 1760 Haygood Dr, Atlanta, GA 30322 USA
基金
美国国家卫生研究院;
关键词
antiviral therapy; CAM; capsid assembly modulator; cccDNA; core inhibitor; DAA; directly acting antiviral; hepatitis B; HBV; drug resistance; CHRONIC HEPATITIS-B; CORE INHIBITOR; GLS4; KETOCONAZOLE; REPLICATION; COMPOUND; EDP-514; LIFE;
D O I
10.1080/17460441.2023.2239701
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction The burden of chronic hepatitis B virus (HBV) results in almost a million deaths per year. The most common treatment for chronic hepatitis B infection is long-term nucleoside analogs (NUC) or one-year interferon-alpha (pegylated or non-pegylated) therapy before or after NUC therapy. Unfortunately, these therapies rarely result in HBV functional cure because they do not eradicate HBV from the nucleus of the hepatocytes, where the covalently closed circular DNA (cccDNA) is formed and/or where the integrated HBV DNA persists in the host genome. Hence, the search continues for novel antiviral therapies that target different steps of the HBV replication cycle to cure chronically infected HBV individuals and eliminate HBV from the liver reservoirs. Areas covered The authors focus on capsid assembly modulators (CAMs). These molecules are unique because they impact not only one but several steps of HBV viral replication, including capsid assembly, capsid trafficking into the nucleus, reverse transcription, pre-genomic RNA (pgRNA), and polymerase protein co-packaging. Expert opinion Mono- or combination therapy, including CAMs with other HBV drugs, may potentially eliminate hepatitis B infections. Nevertheless, more data on their potential effect on HBV elimination is needed, especially when used daily for 6-12 months.
引用
收藏
页码:1031 / 1041
页数:11
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