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.
Wei-Ping Lee  1  2 ,  Keng-Li Lan  3  4 ,  Shi-Xian Liao  5 ,  Yi-Hsiang Huang  5  6  7 ,  Ming-Chih Hou  5  6 ,  Keng-Hsin Lan  5  6  8
Affiliations
  • 1. Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
  • 2. Institute of Biochemistry and Molecular Biology, School of Life Sciences, National Yang-Ming University, Taipei, Taiwan, ROC.
  • 3. Division of Radiation Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
  • 4. Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
  • 5. Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
  • 6. Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
  • 7. Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
  • 8. Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC.
PMID: 30920421 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.

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