In-silico screening of marine fungal metabolites identifies potential FtsZ inhibitors against MDR-tuberculosis through docking and molecular dynamics analysis

Tuberculosis (TB) remains a major global health challenge, intensified by the rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The bacterial cell division protein FtsZ, a key GDPase required for cytokinesis, represents a promising target for novel anti-TB therapeutics. This study aimed to identify potential FtsZ inhibitors among marine fungal metabolites using molecular docking, molecular dynamics (MD) simulations, and MM/GBSA analyses. Docking was performed with AutoDock Vina v1.2.0, followed by 200 ns MD simulations using Desmond to evaluate complex stability. Among 100 screened metabolites, Xanalteric acid II showed the strongest binding affinity (- 10.9 kcal/mol), interacting with Arg140 and Thr130 within the active site, outperforming the co-crystallized ligand (- 9.1 kcal/mol) and moxifloxacin (- 7.7 kcal/mol). The FtsZ-Xanalteric acid II complex exhibited stable RMSD and compact radius of gyration throughout the simulation. MM/GBSA analysis revealed a strong binding free energy (ΔG_bind = - 74.77 ± 4.95 kcal/mol), dominated by van der Waals and lipophilic interactions. PCA, FEL, and DCCM analyses confirmed the structural rigidity and energetic stability of the complex. These findings highlight Xanalteric acid II as a promising marine-derived inhibitor of FtsZ and support the potential of marine metabolites in developing next-generation anti-TB agents.