- 现金
- 62111 元
- 精华
- 26
- 帖子
- 30437
- 注册时间
- 2009-10-5
- 最后登录
- 2022-12-28
|
Ergosterol peroxide inhibits HBV infection by inhibiting the binding of the pre-S1 domain of LHBsAg to NTCP
Hsing Huang 1 , Hsiu-Chen Huang 2 , Wei-Chung Chiou 1 , Lie-Chwen Lin 3 , Jui-Chieh Chen 4 , Hui-Kang Liu 5 , Yu-Heng Lai 6 , Cheng Huang 7
Affiliations
Affiliations
1
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
2
Department of Applied Science, National Tsing Hua University South Campus, Hsinchu, Taiwan; Center for Teacher Education, National Tsing Hua University, Hsinchu, Taiwan.
3
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan.
4
Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan.
5
National Research Institute of Chinese Medicine, Ministry of Health and Welfare, Taipei, Taiwan; Ph. D. Program in the Clinical Drug Development of Herbal Medicine, Taipei Medical University, Taipei, Taiwan.
6
Department of Chemistry, Chinese Culture University, Taipei, Taiwan.
7
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: [email protected].
PMID: 34627935 DOI: 10.1016/j.antiviral.2021.105184
Abstract
Hepatitis B virus (HBV) infection leads to severe liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). More than 257 million individuals are chronically infected, particularly in the Western Pacific region and Africa. Although nucleotide and nucleoside analogues (NUCs) and interferons (IFNs) are the standard therapeutics for HBV infection, none eradicates HBV covalently closed circular DNA (cccDNA) from the infected hepatocytes. In addition, long-term treatment with NUCs increases the risk of developing drug resistance and IFNs may cause severe side effects in patients. Thus, a novel HBV therapy that can achieve a functional cure, or even complete elimination of the virus, is highly desirable. Regarding the HBV life cycle, agents targeting the entry step of HBV infection reduce the intrahepatic cccDNA pool preemptively. The initial entry step in HBV infection involves interaction between the pre-S1 domain of the large hepatitis B surface protein (LHBsAg) and the sodium taurocholate cotransporting polypeptide (NTCP), which is a receptor for HBV. In this study, ergosterol peroxide (EP) was identified as a new inhibitor of HBV entry. EP inhibits an early step of HBV entry into DMSO-differentiated immortalized primary human hepatocytes HuS-E/2 cells, which were overexpressed NTCP. Also, EP interfered directly with the NTCP-LHBsAg interaction by acting on the NTCP. In addition, EP had no effect on HBV genome replication, virion integrity or virion secretion. Finally, the activity of EP against infection with HBV genotypes A-D highlights the therapeutic potential of EP for fighting HBV infection.
Keywords: Entry inhibitor; Ergosterol peroxide; HBsAg; Hepatitis B virus; NTCP.
Copyright © 2021. Published by Elsevier B.V. |
|