In silico analysis to identify potential antitubercular molecules in Morus alba through virtual screening and molecular dynamics simulations

A major obstacle in the treatment of tuberculosis (TB) is to combat the emerging resistant strains of its causing agent i.e. Mycobacterium tuberculosis (MTb). The emergence of multidrug-resistant and extensively drug-resistant -TB strains raise a requirement of new potential anti-tubercular compounds. In this direction, different plant parts of Morus alba were tested against MTb and found to be active with a minimum inhibitory concentration ranging between 125 µg/ml to 31.5 µg/ml. Further to identify the phytochompounds having anti-mycobacterium activity, phytocompounds of the plant were docked against the five MTb proteins (PDB ID: 3HEM, 4OTK, 2QO0, 2AQ1 and 6MNA). Among twenty-two tested phytocompounds, four phytocompounds with effective binding energy (kcal/mol): Petunidin-3-rutinoside (3HEM: -8.2, 4OTK: -6.9, 2QO0: -9.0, 2AQ1: -8.3 and 6MNA:-7.8), Quercetin-3'-glucoside (3HEM:-6.7, 4OTK:-7.6, 2QO0:-7.6, 2AQ1:7.6 and 6MNA:-6.4), Rutin (3HEM:-7.8, 4OTK:-7.5, 2QO0:-9.1, 2AQ1:9.3 and 6MNA:-6.9) and Isoquercitrin (3HEM:-7.3, 4OTK:-6.6, 2QO0:-7.7, 2AQ1:8.3 and 6MNA:-6.6) shows promising activity against all the five target proteins. Further molecular dynamics studies of Petunidin-3-rutinoside with three target proteins 3HEM, 2AQ1 and 2QO0 resulted with low values of average RMSD (3.723 Å, 3.261 Å, and 2.497 Å, respectively) show that the complexes have better conformational stability. The wet lab validation of the current study will pave the new dimensions for the cure of TB patients.Communicated by Ramaswamy H. Sarma.