Dicoumarol, an NQO1 inhibitor, blocks cccDNA transcription by promoting degradation of HBx

• Published in: Journal of hepatology Vol. 74; no. 3; pp. 522 - 534
• Main Authors: Cheng, Sheng-Tao, Hu, Jie-Li, Ren, Ji-Hua, Yu, Hai-Bo, Zhong, Shan, Wai Wong, Vincent Kam, Kwan Law, Betty Yuen, Chen, Wei-Xian, Xu, Hong-Mei, Zhang, Zhen-Zhen, Cai, Xue-Fei, Hu, Yuan, Zhang, Wen-Lu, Long, Quan-Xin, Ren, Fang, Zhou, Hong-Zhong, Huang, Ai-Long, Chen, Juan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2021; Elsevier Science Ltd
• Subjects: Animals; Antiviral activity; Antiviral agents; Antiviral Agents - administration & dosage; cccDNA; Chromatin; Chronic infection; Circular DNA; Degradation; Deoxyribonucleic acid; Dicoumarol; Dicumarol - administration & dosage; Disease Models, Animal; DNA; DNA, Circular - isolation & purification; DNA, Circular - metabolism; HBx; HBX protein; Hep G2 Cells; Hepatitis; Hepatitis B; Hepatitis B surface antigen; Hepatitis B virus; Hepatitis B virus - drug effects; Hepatitis B virus - metabolism; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - metabolism; Hepatitis B, Chronic - virology; Hepatocytes - metabolism; Humans; Liver; Mice; Mice, Inbred C57BL; Mice, Transgenic; NAD; NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors; NAD(P)H Dehydrogenase (Quinone) - genetics; NAD(P)H Dehydrogenase (Quinone) - metabolism; NADPH quinone oxidoreductase; Proteasomes; Protein stabilisation; Proteins; Proteolysis - drug effects; Quinone oxidoreductase; Replication; Trans-Activators - metabolism; Transcription; Transcription, Genetic - drug effects; Transfection; Treatment Outcome; Viral Regulatory and Accessory Proteins - metabolism; Virus Replication - drug effects; Virus Replication - genetics; Protein stabilisation; Hepatitis B virus; cccDNA; Dicoumarol; HBx

Current antiviral therapies help keep HBV under control, but they are not curative, as they are unable to eliminate the intracellular viral replication intermediate termed covalently closed circular DNA (cccDNA). Therefore, there remains an urgent need to develop strategies to cure CHB. Functional s...