Unveiling the binding ballet: A molecular dynamics study on caffeic acid interaction with Ilhéus virus NS2B-NS3 protease complex

Abstract

Ilhéus virus (ILHV), an arbovirus belonging to the Flaviviridae family, poses a significant health threat with limited knowledge about its protein structures. This study aims to fill this gap by using structural analysis and molecular dynamics-based pharmacophore modeling. These advanced molecular tools enable us to develop a robust virtual screening model for identifying potential antiviral drugs against ILHV. The present study used the Robetta protein molecular modeling tool (https://robetta.bakerlab.org), molecular dynamics simulations using GROMACS, molecular docking using AutoDock Vina, and the nAPOLI server for analysis of protein-ligand interactions. Our molecular docking results reveal the remarkable affinity of caffeic acid to act like an allosteric inhibitor by binding the NS2B- NS3 protease. This finding is important as the NS2B-NS3 protease has highly conserved domains among Flavivirus, suggesting that caffeic acid could be a pan-flavivirus antiviral drug. Although this research is in silico, it provides insights into essential molecular interactions, paving the way for targeted drug discovery in the fight against ILHV and related arboviruses.

Keywords:
Ilhéus virus; Caffeic acid; Molecular docking; Molecular dynamics; Drug discovery