Potent virucidal activity of honeybee "Apis mellifera" venom against Hepatitis C Virus

Hepatitis C virus (HCV) is a global viral widespread without an available vaccine to prevent infection. HCV infection can cause serious liver diseases such as hepatocellular carcinoma (HCC). Current treatment of HCV infection depends on the FDA approved direct-acting antivirals (DAAs) which have side effects and expensive. Thus, development of a novel, more efficient, along with affordable pricing anti-HCV agents is still required. The purpose of the present study is to evaluate the antiviral effects of bee venom (BV) from the honeybee Apis mellifera on the HCV replication life cycle. The crude venom and its components were examined for their anti-HCV activities using Huh7it-1 cultured cells and the JFH1 strain of HCV genotype 2a. Results revealed that BV inhibited HCV infection with 50% inhibitory concentration (IC₅₀) of 0.05 ng/ml, while the 50% cytotoxic concentration (CC₅₀) being 20,000 ng/ml. The venom directly blocked HCV/cell entry by acting on virus particles in a dose dependent manner, whereas no interference on the host cells. Furthermore, venom showed no inhibitory effect on HCV replication and release. Interestingly, none of the main BV components including the mast cell degranulating peptide (MCD), mpamin, or the small peptides melittin (MLT) showed anti-HCV activity up to 5 μg/ml. In conclusion, these results suggest that BV has a direct virucidal activity against HCV and may exert its antiviral effect through a non-common peptide(s) or toxin complex within the crude venom. Therefore, the crude BV can be considered as a promising candidate for characterization and development of new and natural anti-HCV therapeutic agents.