Hepatitis C virus (HCV) infection is one of the major public health problems in the world. Even though the new agents are shown to increase the sustained virology response, however, there are still many people who cannot access the therapy due to the high cost. Moreover, the emergence of resistance and side effects presented the necessity to develop alternative treatment agents for HCV infection. Plants of the genus of curcuma are popular among traditional medicines in the world, including Indonesia. They have been used for many herb remedies and reported to possess many biological activities. Several plants from the curcuma genus were known as treatment agents in liver disease and jaundice. Our current study determines antiviral activities of Curcuma domestica, Curcuma xanthorrhiza, and Curcuma heyneana against HCV and further examines the mechanism of actions. Antiviral activity was performed by in vitro culture cells using Huh 7.5it cells and treated with the mixture of extract and virus JFH1. The effects of extracts in HCV life cycle were determined by mode of action analysis to examine the action of substances in the entry or post entry steps. The results revealed that ethanol extract of C. domestica, C. xanthorrhiza, and C. heyneana showed strong anti-HCV activities with IC 50 values of 1.68 ± 0.05, 4.93 ± 0.42 and 5.49 ± 0.59 µg/mL, respectively without any cytotoxicity effect. Mode of action analysis demonstrated that of C. domestica and C. heyneana exhibit HCV in the entry step, while C. xanthorrhiza inhibit in the entry and post entry steps of HCV life cycle. Docking analysis to predict the interaction of curcumin, the main compound of curcuma genus, revealed a strong interaction between curcumin and 4GAG receptor, a protein involved in the entry step of HCV infection. Moreover, it was also reported to possess good interaction with 4EAW, an HCV NS5B, which plays an important role in HCV replication. These results suggested that C. domestica, C. xanthorrhiza, and C. Heyneana possessed strong inhibition against hepatitis C virus, therefore they may be good candidates for anti-HCV agents.

Background Medicinal plants are known to perform many pharmacological actions due to their chemical metabolites, which include antiviral effects. Previously, the extract of Ruta angustifolia was shown to have potential anti-hepatitis C virus (HCV) activity without any cytotoxicity, with a 50% inhibitory concentration of 3.0 μg/mL and a 50% cytotoxicity concentration of >100 μg/mL. Furthermore, the combination of medicinal plants and current anti-HCV agents, such as a direct-acting antiviral agent, was shown to potentiate their overall effectiveness. In the course of this study, the ethanolic extract of R. angustifolia was evaluated for its anti-HCV effects; specifically, the mechanism of action on HCV NS3 and NS5A protease was investigated. Methods Analysis of the use of this extract in conjunction with current NS3 inhibitor drugs, simeprevir (SMV) and telaprevir (TVR), was performed. Anti-HCV activity was performed by in vitro culture of hepatocyte cells. The cells were infected and treated with various concentrations of the sample. HCV inhibition was calculated and CompuSyn software analysis was used to determine the synergistic effect of the combination. Results Results demonstrated that R. angustifolia extract inhibited the post-entry step and decreased the protein levels of HCV NS3 and NS5A. The combination of extract and SMV and TVR mediated a synergistic effect. Conclusions These findings suggest that combining R. angustifolia extract with current anti-HCV drugs should be considered when developing alternative and complementary anti-HCV medicines.

Background: Hepatitis c virus infection is a global health problem which chronically infected 71 million people in the world. This infection has a risk of becoming liver cirrhosis and hepatocellular carcinoma. Since the current HCV therapy has been developed by direct-acting antivirals (DAA), however, most patients get limited access due to the high cost. Therefore, further development anti-HCV agent still greatly needed. Ruta angustifolia is a natural resource which was reported to possess anti-HCV activity. Ribavirin is an antiviral agent used to treat several virus infections, either DNA or RNA. Ribavirin was known to inhibit HCV infection by regulated immune system in host cells and interfering the replication of HCV by inhibit HCV RdRp. Objective: The current study evaluated the combination treatment of R. angustifolia extracts and ribavirin by in vitro culture cells of Huh 7it. Method: The study was conducted under an invitro cell culture of Huh 7it and infected with JFH1a. Result:  The result demonstrated an enhancement effect of the extract by increasing the anti-HCV activity 3.5-fold higher compared to ribavirin alone. The 50% inhibitory concentration of ribavirin by single treatment was 10.43 ± 0.18 µg/mL, while in combination with Ruta angustifolia extract was 2.80 ± 0.03 µg/mL. Further analysis of the combination by CompuSyn software mediated a synergistic effect among the combination with a combination index value of 0.691. Conclusion: These results suggested that combination of Ribavirin and Ruta angustifolia should be considered in developing anti-hepatitis C virus agents.

Hepatitis C virus (HCV) is a major cause of liver disease worldwide and a potential cause of substantial morbidity and mortality in the future. The most recent WHO estimate of the prevalence of HCV infection is 2%, representing 120 million people. Current standard of care is effective in only 50% of the patients, poorly tolerated, and associated with significant side effects and viral resistance. Therefore, a new drugs is needed for the development of complementary and alternative treatment strategies for HCV infection. A variety of medicinal plants have demonstrated antiviral efficacies and some of them possess broad spectrum antiviral activities. In this study, some of Indonesian medicinal plants were evaluated for their anti-HCV activities. Ethanol extracts of 21 samples derived from 19 species of plants that were explored from East Java Region were tested. Anti HCV activities were determined by cell culture method using Huh 7.5 cells and HCV J6/JFH1. The results showed that 6 of 21 samples have potential activity against HCV: Eucalyptus globulus stem (IC 5 : 15.1 µg/ml), Toona sureni leaves (IC 5 : 11 µg/ml), Melicope vitiflora leaves and stem (IC 5 : 9.6 and 15.7 ug/ml, respectively), Melanolepis multiglandulosa stem (IC 5 : 15.5 µg/ml) and Ficus fistulosa leaves (IC5 5 : 23.0 µg/ml). These plant extracts may be good candidates for the development of anti-HCV drugs.