2. Academic Validation
  3. Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry

Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry

  • J Hepatol. 2015 Mar;62(3):541-8. doi: 10.1016/j.jhep.2014.10.040.
Liang-Tzung Lin 1,  Chueh-Yao Chung 2,  Wen-Chan Hsu 3,  Shun-Pang Chang 3,  Ting-Chun Hung 4,  Justin Shields 5,  Rodney S Russell 6,  Chih-Chan Lin 7,  Chien-Feng Li 7,  Ming-Hong Yen 2,  D Lorne J Tyrrell 5,  Chun-Ching Lin 8,  Christopher D Richardson 9
Affiliations

Affiliations

  • 1 Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • 2 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 3 School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
  • 4 Department of Clinical Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
  • 5 Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada.
  • 6 Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
  • 7 Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
  • 8 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: aalin@kmu.edu.tw.
  • 9 Department of Pediatrics and Canadian Center for Vaccinology, Izaak Walton Killam Health Centre, Halifax, Nova Scotia, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. Electronic address: chris.richardson@dal.ca.
PMID: 25450204 DOI: 10.1016/j.jhep.2014.10.040
Abstract

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.

Keywords

Antiviral; Hepatitis C virus; Inhibitor; Liver transplant; Saikosaponin; Virus entry.

Figures
Products