Exploring the Mangrove Based Phytochemicals as Potential Viral RNA Helicase Inhibitors by in silico Docking and Molecular Dynamics Simulation Methods

Abstract

A variety of plant-derived molecular compounds from mangrove plants have attracted attention due to the discovery of their antiviral activity. It has been proven that herbal medicines based on them provide good protection against a number of pathogenic viruses. However, it is necessary to screen these effective antiviral compounds to select those that have fewer harmful side effects. This study aimed to screen several bioactive compounds from mangrove plants that could be used as a viral RNA helicase inhibitor. Fifty-nine compounds were selected from the literature and databases for initial study and screening according to Lipinski's rule of five. The resulting selected compounds were subjected to another round of screening through molecular docking studies with five different pathogenic virus RNA helicase enzymes using the Autodock Vina tool followed by ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis. In addition, the best compound-bound helicase-RNA complexes were included in 50 ns molecular dynamics simulations using Gromacs 5.1.1 software followed by molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) analysis. This comparative study predicts that the phytochemical gedunin is an excellent inhibitor of the RNA helicase enzyme of SARS-CoV-2, followed by Japanese encephalitis virus and hepatitis C virus. The results of the study may lead to the development of antiviral compounds against the RNA helicase enzymes of pathogenic viruses.