Identification of novel inhibitors of HCV NS3 protease genotype 3 subtype B through molecular docking studies of phytochemicals from Boerhavia diffusa L

Abstract

Phytochemicals exert antiviral activity and play a major role in treating hepatitis C virus (HCV) infection. The present work was designed to find out the HCV NS3 protease of genotype 3b inhibitors from a medicinal plant Boerhavia diffusa L. A potent inhibitory effect of recombinant NS3 genotype 3subtypeb catalytic activity was obtained with ethanolic extract of the whole plant by in vitro analysis. Through molecular docking studies it was observed that most of the flavonoids bound deeply in the binding pocket of HCV NS3 protease and interacted with the catalytic triad. The lead moleculesfrom the plant which had anti HCV activity was identified to beliriodendrin, 3,5,6 tri-hydroxyl-4 methoxy flavone7-β-D glucoside, caffeoyl tartaric acid, astragalin, boerhavin A, quercetin, 3,3,5,7 tetra hydroxyl 4 methoxy flavones, 4, 25- secoobscurinervan and 3,5,7,2,5 penta hydroxyl flavones. The best interacted compound which interacted with NS3 was liriodendrin with an energy score of −10.72 kcal/mol. This shows that the phytochemicals especially flavonoids and triterpenoids present in B. diffusa had a direct inhibitory effect on the HCV NS3 protease. The results highlight the potential of B. diffusa as a natural non toxic anti-HCV agent reducing viral counts inside the hepatocytes by inhibiting NS3 protease.From this study it is concluded that these compounds could serve as important inhibitors to block replication of HCV.