Quantum chemical and molecular docking studies on two potential hepatitis C virus inhibitors

Abstract

 Hepatitis C virus (HCV) is responsible for various clinical conditions ranging from acute viral hepatitis to chronic liver disease and cirrhosis, causing liver cancer. The inhibition of HCV NS5B polymerase is a major step towards design of anti-HCV drugs. This study is devoted to two potential inhibitors of NS5B polymerase using quantum chemical and molecular docking methods. The structures of these molecules have been optimized using density functional theory at B3LYP/6–311++G (d,p) level. The vibrational spectral analyses of these two molecules have been performed in detail. The calculated vibrational spectral studies of both the title compounds are in good agreement with previous result. The frontier orbital surfaces and molecular electrostatic potential surfaces have been analyzed. The energy gap between HOMO and LUMO suggest that the compd2 is more reactive than compd1. The molecular electrostatic potential plots suggest the suitable nucleophilic and electrophilic sites in title compounds. Various electronic and thermodynamic parameters of both molecules have been calculated and compared. Finally, the inhibition activity of these compounds with the help of molecular docking studies, against NS5B polymerase enzyme has been explored. The result of docking studies suggests that these compounds are emerging as an effective potent inhibitor of HCV NS5B polymerase and can be useful in the design of novel anti-HCV drugs.