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

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.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.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.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.