Insights into the Inhibition Mechanism of Lipoteichoic Acid Synthase (LtaS) Enzyme by Endophytic Fungal Metabolites: A Molecular Docking and Dynamics Simulation Study for Combatting Drug Resistance

Antimicrobial Resistance (AMR) has spread throughout the world and caused wellknown antibiotics to repeatedly fail to treat common infections. Staphylococcus aureus is a highly concerning pathogen among drug-resistant bacteria. It is the primary cause of life-threatening infections acquired in healthcare settings and the community, particularly those linked to implanted medical devices. The synthesis of lipoteichoic acid has been identified as a potential target for antibacterial treatment due to its essential functions in the proliferation and survival of Gram-positive bacteria. In this research work, we have employed secondary metabolites, particularly coumarins and iso-coumarins which are polyketides derived from endophytic fungi in the inhibition of Lipoteichoic acid synthase (LtaS) enzyme through molecular docking. The objective was to identify a potential drug candidate that could be used as an alternative to antibiotics in treating drug-resistant infections. Pestalustaine B displayed the highest docking score of -8.5 Kcal/mol out of the eleven polyketides that were examined. The ADMET study of Pestalustaine B and Pestalotiopisorin B revealed that both of these metabolites followed Lipinski's rule of five which is an important parameter while considering a compound as a drug candidate. Thus, polyketides indicated their potential as a drug candidate for addressing drug resistance.