Computational design of oleuropein as a potential antifungal agent and enzyme engineering targeting multidrug-resistant fusarium species.

Fusarium species, including Fusarium oxysporum and Fusarium solani, pose significant threats to global agriculture due to their multidrug resistance (MDR), which reduces the efficacy of conventional fungicides. This study investigates the potential of Oleuropein, a natural phenolic compound, as a candidate antifungal agent targeting Fusarium-associated proteins. Molecular docking analysis indicated that oleuropein exhibits favorable binding affinity (- 6.6 kcal/mol) toward key fungal targets, supported by hydrogen bonding and hydrophobic interactions. The stability of the protein-ligand complex, evaluated using Normal Mode Analysis (NMA), suggests a stable interaction profile. Furthermore, in silico mutational analysis of the FoEG1 active site using Hotspot Wizard indicated enhanced binding interactions of oleuropein with selected variants compared to the native enzyme structure.Additionally, molecular dynamic results indicated the stability of ole and mutated enzyme interaction. In contrast to conventional azole-based fungicides, which primarily target ergosterol biosynthesis and are increasingly affected by resistance, oleuropein is predicted to interact with alternative protein targets, suggesting a potentially different mode of action. These findings highlight the utility of computational approaches in identifying natural compounds with antifungal potential and provide a foundation for future experimental validation.