Exploring the therapeutic potential of Polygonum aviculare L. compounds against Dengue virus through Computational methods

Abstract

Introduction

The dengue virus, commonly referred to as DENV, is the primary cause of dengue fever and is a serious health concern worldwide, especially in tropical and subtropical regions. Since DENV's protease NS2B-NS3 is an enzyme necessary for viral transmission, antiviral medications have an adequate probability of being effective. Natural compounds derived from plants like Polygonum aviculare L. which is also commonly known as knot grass or prostate knotweed, have been recognised for their potential antiviral properties

Methods

Initially, the three-dimensional model of NS2B-NS3 protease and the .sdf format structures of knot grass compounds were retreived from PDB and ChEBI databases, respectively which were later proceeded for molecular docking analysis using MOE. The pharmacokinetic analysis was done by utilizing ADMETlab ver. 2.0 and SwissADME servers whereas, the iMODS server was incoporated to evaluate the structural stability and flexibility of the docked complex.

Results

The results of docking analysis revealed significant interactions between knot grass compounds and the NS2B-NS3 protease. The selection of a potential drug candidate from the incorporated compounds was made not merely on the basis of the docking scores but, their pharmacokinetic properties were also examined in this context. The combined results of both of these investigations i.e., docking and pharmacokinetics analysis suggested that (−)-epicatechin exhibited the most stable binding affinity (-5.6924 kcal/mol) and drug-likeness features. These significant outcomes indicated that this compound possessed the notable degrees of drug-likeness attributes. In the end, the structural stability and interaction dynamics of NS2B-NS3 protease-epicatechin docked complex were examined by incorporating the normal mode analysis and multi-scale simulations. The results indicated significant structural stability and flexibility of the complex under study by the evaluations of the elastic network model, eigenvalues, and bfactor maps, among others

Conclusion

On the basis of the outcomes of multi-dimensional computational analyses, it was proposed that (-)-epicatechin could be a potential drug candidate against DENV. However, the actual efficacy of this compound can only be evaluated in the wet-lab and clinical settings. The findings of this study provided a direction towards exploring the medicinal perspectives of various plants-based compounds in order to identify a potential drug against DENV.