Antiviral Activity of the Artocarpus Genus Extracts and Isolated Compounds Artoserichalcone A, B, and C against Hepatitis C: In vitro and in Silico Model

Hepatitis C is a liver disease caused by the Hepatitis C virus (HCV), an RNA virus which is known for its high mutation rate due to a lack of proofreading activity. To date, HCV has been classified into eight genotypes and 93 subtypes. The first major HCV epidemic occurred between the 1930s and 1960s. The standard treatment for HCV is direct-acting antiviral drugs (DAAs), which have a successful rate of 95% among HCV patients. However, there are still found resistance-associated substitutions (RASs) that indicate the challenge to eliminate this disease is still required. This study screened 54 extracts from ten Artocarpus species for anti-HCV activity. The extracts, prepared using N-hexane, dichloromethane, and methanol were tested for their ability to inhibit HCV in Huh7it-1 cells and JFH1a HCV. Furthermore, Artoserichalcone A, B, and C from the Artocarpus sericicarpus (A. sericicarpus) have been subjected to antiHCV assay. The inhibition measurement was detected by DAB staining for infected cells whereas the toxicity assays were conducted using MTT assay. The result of the study revealed that 15 extracts exhibited inhibitory activity against HCV, with six extracts showed a selectivity index (SI) greater than 10. The highest selectivity index score, 85.30, was observed in the methanol extract of A. sericicarpus. Furthermore, the antiHCV screening activity of Artoserichalcone A, B, and C which have been isolated from A. sericicarpus showed the reduction of HCV infection at a single concentration of 10μg/mL by 87.67±3.88%; 70.55±4.84%; and 81.51±0.97%, respectively. These results indicate that Artocarpus sericicarpus is a promising source of natural antiviral therapeutic agents against HCV and its compounds Artoserichalcone A, B, and C inhibited HCV infection by more than 70 percent at a concentration of 10μg/mL. In silico study revealed that Artoserichalcone A-C demonstrated a deeply binding interaction with NS3 protease of HCV.