Exploring the synergistic therapeutic potential of Morus alba extract in tuberculosis: A computational analysis

Objectives: This study validates the synergistic impact hypothesis of Morus alba phytocompounds on Mycobacterium via molecular docking and simulation. Methods: Phytocompounds (Petunidin-3-rutinoside, Beta-sitosterol, Ecdysterone, Quercetin-3′-glucoside, Quercitrin, Rutin, Scopolin) were tested against key metabolic proteins (MmpL3, DprE1, UgpABCE transporter, porins, OmpATb) of Mycobacterium. Additional proteins (CmaA2, oxidoreductase, FABH, Enoyl-ACP reductase, LpqN) were also included. Docked complexes were analyzed via MD trajectories (RMSD, RMSF, hydrogen bonds) over 100 ns. Results: Binding affinity of phytocompounds with 1UUN (Beta-sitosterol: −9.12692, Ecdysterrone:-12.11162 kcal/mol) and 2KGS (Beta-sitosterol: −6.93) reflects the easy entry of phytocompounds. Phytocompounds interact within cells, inhibiting metabolic pathways and microbial growth. Beta-sitosterol (−7.1 kcal/mol) affects the mycolic acid transfer. Beta-sitosterol (−11.21 kcal/mol) and Ecdysterrone (−9.15 kcal/mol) affect the ribose oxidase pathway. Both compounds also show affinity with UgpABCE transporter. During simulation studies, results showed that the average protein RMSD for the 6MNA-Beta-sitosterol, 6MNA-Scopolin, 4P8T-Beta-sitosterol, and 4P8T-Ecdysterone complexes were 1.87 Å, 2.28 Å, 2.34 Å, and 2.61 Å, respectively. The stability of each complex in dynamic states is ensured by low and steady RMSD variance. In addition, we have endeavored to prove the hypothesis of synergistic application by incorporating our latest findings into the data. Conclusions: Concept of synergistic impact of phytocompounds can be a promising source of treatment after proper lab validation.