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.
