Structure-Based Screening of Natural Products Against DprE1 of Mycobacterium Tuberculosis: An in-Silico Drug-Discovery Study

Tuberculosis caused by the mycobacterium tuberculosis is remain major infectious disease and multidrug resistance strains leads to limit the therapeutic options(1). Decaprenyl phosphoryl-β-D-ribose 2′-epimerase 1 (DprE1) is a flavoprotein involved in the biosynthesis of the decaprenyl phosphoryl arabinose precursor required for the mycobacterium cell wall(2). DprE1 absence in human make it best target for drug discovery for Mycobacterium. This study aims to computationally select the best natural product as a potential inhibitor against DprE1 proteins using Docking, interaction and drug likeliness properties. The crystal structure of DprE1 was obtained from the protein data bank. 1050 phytochemicals selected and after screening 92 were pass the AMDET analysis. These 92 compounds structure downloaded from PubChem. Naturally present ligand in the DprE1 structure used as a reference for binding site assessment and docking validation. Docking is performed by AutoDock vina 1.5.7 and interaction is visualized by BIOVIDIA Discovery Studio 2021. Drug-likeness and pharmacokinetic characteristics were subsequently assessed using ADMET lab3.0. Docking analysis identified the Genistein is a top ranked with the binding affinity 8.2 kcal/mol followed by Kaempferol has 8.1 kcal/mol with binding-site occupancy, and interactions with functionally relevant residues. ADMET analysis further evaluate the drug likeliness and physiochemical properties. The computational study identified he natural compounds binding with the DprE1 and the top compounds serve as best candidate for subsequent biochemicals and microbiological evaluation. However, docking predictions alone cannot establish DprE1 inhibition or anti-tubercular efficacy, and experimental validation is required.