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

Liang Tzung Lin, Chueh Yao Chung, Wen Chan Hsu, Shun Pang Chang, Ting Chun Hung, Justin Shields, Rodney S. Russell, Chih Chan Lin, Chien Feng Li, Ming Hong Yen, D. Lorne J Tyrrell, Chun Ching Lin, Christopher D. Richardson

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)541-548
Number of pages8
JournalJournal of Hepatology
Volume62
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

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Virus Internalization
Terpenes
Hepacivirus
Virus Diseases
Bupleurum
Antiviral Agents
Life Cycle Stages
Hepatocytes
saikosaponin
Hepatovirus
Infection
Virion
Liver Transplantation
Hepatocellular Carcinoma
Glycoproteins
Vaccines
Genotype
RNA

Keywords

  • Antiviral
  • Hepatitis C virus
  • Inhibitor
  • Liver transplant
  • Saikosaponin
  • Virus entry

ASJC Scopus subject areas

  • Hepatology

Cite this

Lin, L. T., Chung, C. Y., Hsu, W. C., Chang, S. P., Hung, T. C., Shields, J., ... Richardson, C. D. (2015). Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry. Journal of Hepatology, 62(3), 541-548. https://doi.org/10.1016/j.jhep.2014.10.040

Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry. / Lin, Liang Tzung; Chung, Chueh Yao; Hsu, Wen Chan; Chang, Shun Pang; Hung, Ting Chun; Shields, Justin; Russell, Rodney S.; Lin, Chih Chan; Li, Chien Feng; Yen, Ming Hong; Tyrrell, D. Lorne J; Lin, Chun Ching; Richardson, Christopher D.

In: Journal of Hepatology, Vol. 62, No. 3, 01.03.2015, p. 541-548.

Research output: Contribution to journalArticle

Lin, LT, Chung, CY, Hsu, WC, Chang, SP, Hung, TC, Shields, J, Russell, RS, Lin, CC, Li, CF, Yen, MH, Tyrrell, DLJ, Lin, CC & Richardson, CD 2015, 'Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry', Journal of Hepatology, vol. 62, no. 3, pp. 541-548. https://doi.org/10.1016/j.jhep.2014.10.040
Lin, Liang Tzung ; Chung, Chueh Yao ; Hsu, Wen Chan ; Chang, Shun Pang ; Hung, Ting Chun ; Shields, Justin ; Russell, Rodney S. ; Lin, Chih Chan ; Li, Chien Feng ; Yen, Ming Hong ; Tyrrell, D. Lorne J ; Lin, Chun Ching ; Richardson, Christopher D. / Saikosaponin b2 is a naturally occurring terpenoid that efficiently inhibits hepatitis C virus entry. In: Journal of Hepatology. 2015 ; Vol. 62, No. 3. pp. 541-548.
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AU - Richardson, Christopher D.

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N2 - 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.

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