Virtual Screening of Telaprevir and Danoprevir Derivatives for Hepatitis C Virus NS3/4A Protease Inhibitors

Abstract

Background: The NS3/4A protease is a common target for inhibiting hepatitis C virus (HCV) infection. Telaprevir and danoprevir have promising activity in combating these virus-associated infections and are used as HCV protease inhibitors. Objective: In this study, we have found different tested derivative compounds for developing various HCV NS3/4A protease inhibitors by designing the chemical structures of telaprevir and danoprevir. Methods: In silico studies were carried out to find better drug candidatures from these derivative compounds. The docking studies were performed on HCV NS3/4A protease receptors (PDB: 3SV6 & 5EQR) using Autodock vina. DFT, global reactivity, ADME (Absorption, distribution, metabolism & excretion), and toxicity analysis were also performed for these designed compounds. The stability of the protein-ligand complexes was quantified by MD simulation and MMPBSA studies. Results: 16 derivatives (four as telaprevir and twelve as danoprevir) have satisfied higher binding affinity of interaction with NS3/4A protease, compared to telaprevir and danoprevir. These compounds have also passed all rules of drug candidature to serve as the best HCV inhibitors. Conclusion: These 16 ligands can be effective inhibitors against HCV NS3/4A protease. These ligands must obey the drug candidate behavior by in vitro and in vivo analysis to inhibit HCV infection.