D-cycloserine, a potential candidate for reducing Hepatitis B virus cccDNA in vitro

IF 1.6 4区医学 Q3 BIOCHEMICAL RESEARCH METHODS

Journal of virological methods Pub Date : 2025-04-28 DOI:10.1016/j.jviromet.2025.115172

Yongwook Choi , Yong Kwang Park , Wonhee Hur , Gahee Kim , Songmee Bae

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引用次数: 0

Abstract

Hepatitis B virus (HBV) is a 3.2 kb hepatotropic DNA that possesses a unique episomal DNA form known as covalently closed circular DNA (cccDNA). cccDNA is the major risk factor for persistent HBV infection and consequently causes chronic liver diseases such as hepatitis, cirrhosis, and hepatocellular carcinoma. To prevent the progression of liver disease, eradication of HBV, especially cccDNA, is essential. In this study, we established a drug screening system using artificial recombinant HBV cccDNA (rcccDNA), which is regulated by a loxP-HBV genome and CRE expression. To identify potential drugs targeting cccDNA, a total of 379 antiviral reagents were tested. Among them, several chemicals including danoprevir, L- and D-cycloserine, phenytoin sodium, amantadine, and germacrone showed a decrease in cccDNA levels. Especially, D-cycloserine diminished the secretion of HBV antigens and induced cccDNA degradation in the HBV infection system. This screening system helps to develop the therapeutic drug target to cccDNA This screening system may help develop therapeutic drugs targeting cccDNA.

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d -环丝氨酸：体外减少乙型肝炎病毒cccDNA的潜在候选物

乙型肝炎病毒（HBV）是一种3.2 kb的嗜肝性DNA，具有独特的外泌体DNA形式，称为共价闭合环状DNA （cccDNA）。cccDNA是持续性HBV感染的主要危险因素，并因此导致慢性肝病，如肝炎、肝硬化和肝细胞癌。为了预防肝脏疾病的进展，根除HBV，特别是cccDNA是必不可少的。在本研究中，我们建立了一个人工重组HBV cccDNA （rcccDNA）的药物筛选系统，该系统由loxP-HBV基因组和CRE表达调控。为了鉴定靶向cccDNA的潜在药物，共测试了379种抗病毒试剂。其中，达诺韦、L-环丝氨酸和d -环丝氨酸、苯托英钠、金刚烷胺和杰玛酮等几种化学物质的cccDNA水平下降。特别是d -环丝氨酸减少了HBV抗原的分泌，诱导了HBV感染系统中cccDNA的降解。该筛选系统有助于开发靶向cccDNA的治疗药物，有助于开发靶向cccDNA的治疗药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of virological methods 医学-病毒学

CiteScore

5.80

自引率

0.00%

发文量

209

审稿时长

41 days

期刊介绍： The Journal of Virological Methods focuses on original, high quality research papers that describe novel and comprehensively tested methods which enhance human, animal, plant, bacterial or environmental virology and prions research and discovery. The methods may include, but not limited to, the study of: Viral components and morphology- Virus isolation, propagation and development of viral vectors- Viral pathogenesis, oncogenesis, vaccines and antivirals- Virus replication, host-pathogen interactions and responses- Virus transmission, prevention, control and treatment- Viral metagenomics and virome- Virus ecology, adaption and evolution- Applied virology such as nanotechnology- Viral diagnosis with novelty and comprehensive evaluation. We seek articles, systematic reviews, meta-analyses and laboratory protocols that include comprehensive technical details with statistical confirmations that provide validations against current best practice, international standards or quality assurance programs and which advance knowledge in virology leading to improved medical, veterinary or agricultural practices and management.