The investigation of antiviral mechanisms of chitosan nanoparticles encapsulating curcumin against Hepatitis C Virus genotype – 4a on human hepatoma cell lines

Abstract

Hepatitis C virus is the fifth common disease in the world with more than 170 infected people worldwide and poses high risk among Egyptian population as they are likely to develop severe liver injury and hepatocellular carcinoma. Nevertheless, current double and triple treatments with direct acting antivirals (DAAs) were recently reported to cause several side effects and thereby effective, less toxic antiviral agents are needed. Accordingly, this study aims at coupling in silico approaches with in vitro analysis in order to investigate and compare the role of some natural and synthetic antivirals; curcumin, chitosan nanoparticles (CSNPs) and chitosan encapsulating curcumin nanocomposite against HCV-G4a replication in Huh7.5 cells and viral entry in Huh7 cells. Thereby, the selected compounds were subjected to molecular docking studies to determine their binding affinity towards NS3 protease, NS5A and NS5B polymerases prior to investigating their antiviral mechanisms against viral replication and viral entry. Additionally, the activity of such compounds was examined on both the molecular level on the targeted viral genes as well as the protein level on the viral core protein. Accordingly, it is expected to obtain reduction in viral replication as well as obstruction of viral entry after exploiting these compounds, especially the curcumin chitosan nanocomposite which suggests their potential roles as alternative, novel, safe and effective antiviral agents.