Inhibition of HCV RNA-dependent RNA polymerase activity by aqueous extract from Fructus Ligustri Lucidi

The development of effective antiviral drugs against hepatitis C virus (HCV) continues to be needed, since neither vaccines nor broadly effective therapeutic agents are available. HCV RNA-dependent RNA polymerase (NS5B) is strictly required for viral replication and thus represents an attractive target. Here, aqueous extracts from five traditional Chinese medicines were tested for their ability to inhibit NS5B activity by reporter assays using cell-based NS5B activity detecting systems. Among them, aqueous extract from Fructus Ligustri Lucidi exhibited a promising result, dose-dependent inhibition of the luciferase activity, an indicator of intracellular NS5B activity (p < 0.001), in the absence of cytotoxicity. Further Quantitative RT-PCR assays and Western blot analysis showed aqueous extract from Fructus Ligustri Lucidi inhibited intracellular NS5B-catalyzed RNA synthesis dose-dependently (p < 0.001) without affecting intracellular NS5B expression. Subsequent in vitro NS5B assays revealed that this extract could directly inhibit NS5B activity. Taken together, these results indicated that Fructus Ligustri Lucidi might offer a promising source of antiviral drugs against HCV NS5B. Purification of the active compound(s) and antiviral effect are clearly required in the future.