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



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.



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.



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.



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.



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.
