Tropheryma whipplei is main causative agent of whipple ailment as it is multisystemic fatal disorder and there is still need of developing best regimens for its regulation. To control its spread and to treat it effectively three drugs were identified in this study by deploying pharmaco-informatic approach. 2-amino-7-fluoro-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide (2APC), Nicotinamide mononucleotide(NMN), and Riboflavin monophosphate(RFMP) were found to be putative drugs. 2APC and NMN inhibits activity of DNA Ligase enzyme of this bacterium and effective in impairing replication and repair mechanisms, while RFMP exhibits inhibitory effect on Chorismate synthase that leads impairment of amino acid metabolism or biosynthesis. In this study effective alignment tools like BLAST, CDART, CD-HIT were used to select enzymes. Phyre2 based on HMM algorithm is deployed to find best structural models of selected enzymatic proteins. Auto Dock-Vina tool is used for docking and scoring binding energies of these drugs with considered enzymatic domains. 2APC and NMN inhibiting DNA Ligase exhibits -8.3 and -8.2 kcal/mol respectively while RFMP inhibiting Chorismate synthase -7.3 kcal/mol. This intensive and novel study is easy, fast, and useful in predicting drugs by In-silico approach. This intensive pharmaco-informatic study reveals that 2-amino-7-fluoro-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxamide, Nicotinamide mononucleotide, and Riboflavin mono phosphate considered as putative drugs and they can be used for further wet-lab validation. All the pharmacophores of analyzed drugs were found to be perfectly interacting with enzymatic assemblies to inhibit them. This is easy and fast method to predict drug and even effective against organisms like Tropheryma whipplei having reduced genome.
Keywords: Drug, In-silico, Binding energy, Allignment, DNA-Ligase, Chorismate synthase, Docking