期刊
JOURNAL OF HEPATOLOGY
卷 62, 期 3, 页码 541-548出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2014.10.040
关键词
Hepatitis C virus; Virus entry; Inhibitor; Antiviral; Saikosaponin; Liver transplant
资金
- Taipei Medical University [TMU101-AE3-Y19]
- Ministry of Science and Technology of Taiwan [MOST101-2320-B-038-038-MY2]
- Canadian Institutes of Health [CIHR-MOP-114949]
- Canadian Liver Foundation
- Department of Chinese Medicine and Pharmacy, Ministry of Health and Welfare of Taiwan [CCMP101-RD-029]
- Alberta Innovates [201201140] Funding Source: researchfish
Background & Aims: A vaccine against hepatitis C virus (HCV) is unavailable and cost-effective antivirals that prevent HCV infection and re-infection, such as in the transplant setting, do not exist. In a search for novel and economical prophylactic agents, we examined the antiviral activity of saikosaponins (SSa, SSb2, SSc, and SSd) from Bupleurum kaoi root (BK) as entry inhibitors against HCV infection. Methods: Infectious HCV culture systems were used to examine the effect of saikosaponins on the complete virus life cycle (entry, RNA replication/translation, and particle production). Antiviral activity against various HCV genotypes, clinical isolates, and infection of primary human hepatocytes were also evaluated. Results: BK and the saikosaponins potently inhibited HCV infection at non-cytotoxic concentrations. These natural agents targeted early steps of the viral life cycle, while leaving replication/translation, egress, and spread relatively unaffected. In particular, we identified SSb2 as an efficient inhibitor of early HCV entry, including neutralization of virus particles, preventing viral attachment, and inhibiting viral entry/fusion. Binding analysis, using soluble viral glycoproteins, demonstrated that SSb2 acted on HCV E2. Moreover, SSb2 inhibited infection by several genotypic strains and prevented binding of serum-derived HCV onto hepatoma cells. Finally, treatment with the compound blocked HCV infection of primary human hepatocytes. Conclusions: Due to its potency, SSb2 may be of value for development as an antagonist of HCV entry and could be explored as prophylactic treatment during the course of liver transplantation. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
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