| Autor: |
Fang Ren, Xiao Yang, Zhong-Wen Hu, Vincent Kam Wai Wong, Hong-Yan Xu, Ji-Hua Ren, Shan Zhong, Xiao-Jiong Jia, Hui Jiang, Jie-Li Hu, Xue-Fei Cai, Wen-Lu Zhang, Fang-Long Yao, Hai-Bo Yu, Sheng-Tao Cheng, Hong-Zhong Zhou, Ai-Long Huang, Betty Yuen Kwan Law, Juan Chen |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
EBioMedicine, Vol 49, Iss , Pp 232-246 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2352-3964 |
| DOI: |
10.1016/j.ebiom.2019.10.022 |
| 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: |
Directory of Open Access Journals |
| Externí odkaz: |
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