Major royal-jelly protein 2 and its isoform X1 are two novel safe inhibitors for hepatitis C and B viral entry and replication.

Infections with HCV and HBV are serious worldwide health problems. Here, we report the anti-HCV and -HBV proficiency of Apis mellifera major royal-jelly protein (MRJP) 2 and its isoform X1. The efficiency of these proteins was evaluated in vitro and their safety was examined in vivo in comparison with Sofosbuvir (SOF) drug. Various in-silico methodologies were achieved for better understanding the antiviral mechanism of these MRJPs. Results proved their precluding ability to the viral receptors, CD81 and scavenger receptor class B type I (SR-B1). In addition, they targeted HCV-NS3/NS4A protease, HCV-NS5B polymerase, and HBV-polymerase (DNA-dependent DNA polymerase, and reverse transcriptase). Co-treatment with these proteins exerted different efficiencies toward CD81 and SR-B1 (synergistic), HBV-enzymes (antagonistic), and HCV-enzymes (either additive or synergistic). The studied proteins maximized their antiviral effect by their safety and superior potency to SOF. Collectively, these outcomes will shed the light on MRJP2 and its isoform X1 as two promising safe-inhibitors for both HCV and HBV.