Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production
| Autor: | Xiaojiong Jia, Juan Chen, Shan Zhong, Hai-Bo Yu, Wenlu Zhang, Fang Ren, Sheng-Tao Cheng, Xiao Yang, Zhong-Wen Hu, Hong-Yan Xu, Betty Yuen Kwan Law, Ji-Hua Ren, Xue-Fei Cai, Ailong Huang, Fang-Long Yao, Hui Jiang, Jieli Hu, Hong-Zhong Zhou, Vincent Kam Wai Wong |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
HBsAg Hepatitis B virus Research paper Transcription Genetic lcsh:Medicine Mice Transgenic Biology medicine.disease_cause Virus Replication Models Biological General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine In vivo Hepatitis B surface antigen (HBsAg) medicine Anti-HBV drugs Animals Humans Viremia Seroconversion Promoter Regions Genetic lcsh:R5-920 Hepatitis B Surface Antigens Nucleoside analogue lcsh:R virus diseases Promoter General Medicine cccDNA Hep G2 Cells Virology In vitro digestive system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology 6-Aminonicotinamide 6-Aminonicotinamide (6-AN) 030220 oncology & carcinogenesis lcsh:Medicine (General) Biomarkers medicine.drug |
| Zdroj: | EBioMedicine EBioMedicine, Vol 49, Iss, Pp 232-246 (2019) |
| ISSN: | 2352-3964 |
| Popis: | Background: Hepatitis B surface antigen (HBsAg) is one of the important clinical indexes for hepatitis B virus (HBV) infection diagnosis and sustained seroconversion of HBsAg is an indicator for functional cure. However, the level of HBsAg could not be reduced by interferons and nucleoside analogs effectively. Therefore, identification of a new drug targeting HBsAg is urgently needed.Methods: In this study, 6-AN was screened out from 1500 compounds due to its low cytotoxicity and high antiviral activity. The effect of 6-AN on HBV was examined in HepAD38, HepG2-NTCP and PHHs cells. In addition, the antivirus effect of 6-AN was also identified in mouse model.Findings: 6-AN treatment resulted in a significant decrease of HBsAg and other viral markers both in vitro and in vivo. Furthermore, we found that 6-AN inhibited the activities of HBV SpI, SpII and core promoter by decreasing transcription factor PPARα, subsequently reduced HBV RNAs transcription and HBsAg production.Interpretation: We have identified a novel small molecule to inhibit HBV core DNA, HBV RNAs, HBsAg production, as well as cccDNA to a minor degree both in vitro and in vivo. This study may shed light on the development of a novel class of anti-HBV agent. Keywords: Hepatitis B virus, Hepatitis B surface antigen (HBsAg), 6-Aminonicotinamide (6-AN), Anti-HBV drugs |
| Databáze: | OpenAIRE |
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