title: Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry.
abstract: OBJECTIVE
  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.
authors.affiliation: 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.
authors.forename: Liang-Tzung
authors.initials: LT
authors.lastname: Lin
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chueh-Yao
authors.initials: CY
authors.lastname: Chung
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wen-Chan
authors.initials: WC
authors.lastname: Hsu
authors.affiliation: School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shun-Pang
authors.initials: SP
authors.lastname: Chang
authors.affiliation: Department of Clinical Pathology, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Ting-Chun
authors.initials: TC
authors.lastname: Hung
authors.affiliation: Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada.
authors.forename: Justin
authors.initials: J
authors.lastname: Shields
authors.affiliation: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada.
authors.forename: Rodney S
authors.initials: RS
authors.lastname: Russell
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chih-Chan
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Medical Research, Chi-Mei Medical Center, Tainan, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
authors.affiliation: Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Yen
authors.affiliation: Li Ka Shing Institute of Virology, Edmonton, Alberta, Canada.
authors.forename: D Lorne J
authors.initials: DL
authors.lastname: Tyrrell
authors.affiliation: 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.
authors.forename: Chun-Ching
authors.initials: CC
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Richardson
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D029972:Bupleurum; D002460:Cell Line; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology*; D006526:Hepatitis C / Q000517:prevention & control; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D016031:Liver Transplantation; D008297:Male; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology / Q000633:toxicity; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D014771:Virion / Q000187:drug effects; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C051274:Bupleurum root extract; D010936:Plant Extracts; D012503:Saponins; D009828:Oleanolic Acid; C025759:saikosaponin D
keywords: Antiviral; Hepatitis C virus; Inhibitor; Liver transplant; Saikosaponin; Virus entry