Insight into novel inhibitors from against Cholera via pharmacoinformatics and molecular dynamics simulation approaches.

The underdeveloped countries with large populations are facing a grave global threat in the form of cholera. , the etiologic agent of Cholera has drawn attention recently due to antimicrobial resistance and resulting outbreaks that necessitates establishment of novel medications to counteract virulence and viability of the pathogen. Roxb. (Malvaceae) is an ethnomedicinally important tree, which harbors a good number of bioactive phytocompounds. In the present study, 53 phytocompounds of were screened against the promising target ToxT of employing structure-based drug design approach that revealed three lead compounds, viz., 4,4,5,8-Tetramethylchroman-2-ol (-8.2 kcal/mol), Beta-Bisabolol (-8.2 kcal/mol) and Ledol (-8.7 kcal/mol) with satisfactory ADMET properties. Molecular dynamics simulation for 150 ns unveiled notable compactness and structural stability for the lead compounds considering RMSD, RMSF, Rg, MolSA, PSA and protein-ligand contacts parameters. Molecular mechanics-based MM/GBSA binding energy calculation revealed Beta-Bisabolol (-66.74 kcal/mol) to have better scores than 4,4,5,8-Tetramethylchroman-2-ol (-47.42 kcal/mol) and Ledol (-65.79 kcal/mol). Enzymes were mostly found as drug target class, and Nabilone was found as a structurally similar analog for 4,4,5,8-Tetramethylchroman-2-ol. These discoveries could aid in revealing new antibacterial medications targeting ToxT to combat Cholera.Communicated by Ramaswamy H. Sarma.