Molecular docking, simulations of animal peptides against the envelope protein of Dengue virus

Abstract

Peptides are biologically active, small molecules with high specificity in its mode of action that can be effective at nanomolar concentrations. Peptide-based antiviral medicines have already been licensed and used to treat human immunodeficiency virus (HIV), influenza virus and hepatitis C virus. So far, no peptide drug has been approved for antiviral treatment against Dengue virus, and many are under clinical trials. Therefore, developing a reasonable peptide against the Dengue virus Envelope protein structure will be a successful strategy for treating Dengue. Hence, we investigated protein-protein docking interactions between 215 peptides retrieved from the AVP database against the envelope protein using Cluspro and HADDOCK followed by the evaluation of their allegenicity, toxicity and physicochemical characteristics investigation. Further validation of the protein–peptide complexes was performed with Molecular dynamics simulations and Molecular Mechanics Poisson–Boltzmann surface area (MMPBSA) analysis on the hit inhibitors. This study revealed that Indolicidin (−75.026 ± 1.54 KJ/mol) and Human Neutrophil peptide-1 (−71.6551 ± 2.112 KJ/mol) shows higher negative ΔG binding implicating their relative stabilization in the protein–peptide interactions during 100 ns of dynamic simulations. Also, both the peptides exhibited desirable physicochemical properties and were nonallergenic. Hence, we further aim to test these peptides by in vitro and in vivo studies to confirm their efficacy against Dengue virus. Communicated by Ramaswamy H. Sarma