Choi Yongwook, Park Yong Kwang, Hur Wonhee, Kim Gahee, Bae Songmee
Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea.
Division of Chronic Viral Disease Research, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Chungbuk, South Korea.
J Virol Methods. 2025 Jul;336:115172. doi: 10.1016/j.jviromet.2025.115172. Epub 2025 Apr 28.
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.
乙型肝炎病毒（HBV）是一种3.2 kb的嗜肝DNA病毒，具有一种独特的游离型DNA形式，称为共价闭合环状DNA（cccDNA）。cccDNA是HBV持续感染的主要危险因素，进而导致慢性肝病，如肝炎、肝硬化和肝细胞癌。为防止肝病进展，根除HBV，尤其是cccDNA至关重要。在本研究中，我们建立了一种利用人工重组HBV cccDNA（rcccDNA）的药物筛选系统，该rcccDNA受loxP-HBV基因组和CRE表达调控。为鉴定靶向cccDNA的潜在药物，共测试了379种抗病毒试剂。其中，包括达诺普韦、L-和D-环丝氨酸、苯妥英钠、金刚烷胺和莪术二酮在内的几种化学物质显示出cccDNA水平降低。特别是，D-环丝氨酸减少了HBV抗原的分泌，并在HBV感染系统中诱导了cccDNA降解。该筛选系统有助于开发针对cccDNA的治疗药物靶点。该筛选系统可能有助于开发针对cccDNA的治疗药物。
