Abstract
Hepatitis C virus (HCV) is an RNA virus that is easy to mutate and high risk of resistance. The vaccine for HCV has not been provided yet, and the current treatment is very expensive. To provide alternative and complementary antiviral from plants, this study evaluated the activities of Piper betle (P. betle) against HCV and its combination with existing antiviral drugs, Ribavirin and Simeprevir. The antiviral inhibition was identified by in vitro culture using Huh7it-1 cells and JFH1a HCV. Moreover, the phytochemistry profile was also determined by Thin Layer Chromatography (TLC) and High-Performance Liquid Chromatography (HPLC). The result showed that the ethanol extract of P. betle was possess strong activity with an IC50 value of 0.08 ± 0.028 µg/mL. The mechanism of action revealed the extract dominantly inhibit in the post-entry steps. Furthermore, the combination of P. betle extract with simeprevir increased its anti-HCV activity, however, no effect was observed in the combination with ribavirin. The Western blotting analysis was shown inhibition of NS3 protein levels in a dose-dependent manner. Phytochemistry evaluation was shown for the extract containing flavonoids, polyphenols, and alkaloids. These results suggested that the ethanolic extract of P. betle could be a good candidate for the development or an alternative to anti-HCV drugs.
 Keywords: Hepatitis C Virus, Piper betle, Medicinal plants, Simeprevir, Ribavirin, Medicine.
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