Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production
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 e...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-11-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306863 |
| _version_ | 1818305779546980352 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Fang Ren |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-13T06:32:01Z |
| format | Article |
| id | doaj.art-5b83bc26c0a343ab9bfcf84c5e2973d0 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-13T06:32:01Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-5b83bc26c0a343ab9bfcf84c5e2973d02022-12-21T23:56:36ZengElsevierEBioMedicine2352-39642019-11-0149232246Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg productionFang Ren0Xiao Yang1Zhong-Wen Hu2Vincent Kam Wai Wong3Hong-Yan Xu4Ji-Hua Ren5Shan Zhong6Xiao-Jiong Jia7Hui Jiang8Jie-Li Hu9Xue-Fei Cai10Wen-Lu Zhang11Fang-Long Yao12Hai-Bo Yu13Sheng-Tao Cheng14Hong-Zhong Zhou15Ai-Long Huang16Betty Yuen Kwan Law17Juan Chen18The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Room 704a-02, Block H, Macau, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaThe Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Room 704a-02, Block H, Macau, China; Corresponding authors.The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Room 617, College of Life Sciences Building, 1 YiXueYuan Road, YuZhong District, Chongqing 400016, China; Corresponding authors.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 drugshttp://www.sciencedirect.com/science/article/pii/S2352396419306863 |
| spellingShingle | 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 Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production EBioMedicine |
| title | Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production |
| title_full | Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production |
| title_fullStr | Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production |
| title_full_unstemmed | Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production |
| title_short | Niacin analogue, 6-Aminonicotinamide, a novel inhibitor of hepatitis B virus replication and HBsAg production |
| title_sort | niacin analogue 6 aminonicotinamide a novel inhibitor of hepatitis b virus replication and hbsag production |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306863 |
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