Antiviral effect of saikosaponin B2 in combination with daclatasvir on NS5A resistance-associated substitutions of hepatitis C virus

J Chin Med Assoc. 2019 May;82(5):368-374. doi: 10.1097/JCMA.0000000000000095.

Abstract

Background: Hepatitis C virus (HCV) is a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The rapid progress in the development of direct-acting antivirals has greatly elevated the cure rate to ≥95% in recent years. However, the high cost of treatment is not affordable to patients in some countries, necessitating the development of less expensive treatment.

Methods: We adopted a cell culture-derived HCV system to screen a library of the pure compounds extracted from herbs deposited in the chemical bank of the National Research Institute of Chinese Medicine, Taiwan.

Results: We found that saikosaponin B2 inhibited viral entry, replication, and translation. Saikosaponin B2 is a plant glycoside and a component of xiao-chai-hu-tang, a traditional Chinese herbal medicine extracted from the roots of Bupleurum falcatum. It also inhibited daclatasvir-resistant mutant strains of HCV, especially in combination with daclatasvir.

Conclusion: Our results may aid the development of a new combination therapy useful for patients with HCV who are intolerant or refractory to the currently available medications, including pegylated interferon and direct-acting antiviral agents.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Carbamates
  • Cells, Cultured
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Hepacivirus / drug effects
  • Hepatitis C / drug therapy*
  • Humans
  • Imidazoles / administration & dosage
  • Imidazoles / pharmacology*
  • Oleanolic Acid / administration & dosage
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Pyrrolidines
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • Valine / analogs & derivatives
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / genetics
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Saponins
  • Viral Nonstructural Proteins
  • Oleanolic Acid
  • NS-5 protein, hepatitis C virus
  • Valine
  • daclatasvir
  • saikosaponin D