Repurposing of drug molecules from FDA database against Hepatitis C virus E2 protein using ensemble docking approach.

Abstract

Hepatitis C virus, a member of the Flaviviridae family and genus Hepacivirus, is an enveloped, positively single stranded RNA virus. Its surface consists of a heterodimer of E1 and E2 proteins which play a crucial role in receptor binding and membrane fusion. In this study we have used in silico virtual screening by utilizing ensemble docking on the approved drugs. These drugs can bind with high efficiency to the 36 prominent conformations of the CD81 binding site clustered from a total of 3µs MD simulation data on the E2 protein. We started with 9213 compounds from the FDA list of drugs and progressively came down to 5 compounds which have been seen to bind with very high efficiency to not only all the conformations but also the two predicted druggable pockets that encompass the CD81 binding site. MM/PBSA binding energy calculations also point to the highly stable interaction of the compounds to the E2 protein. This study may in future broaden the arsenal of therapeutics for use against HCV infection and lead to more effective care against the virus.