Comprehensive molecular docking and antifungal activity analysis of Moringa extracts targeting Candida auris...

Candida auris is an emerging multidrug-resistant fungal pathogen posing serious global healthcare challenges due to its persistence, frequent misidentification, and resistance to all major antifungal drugs. This study aimed to explore natural therapeutic alternatives by investigating the antifungal and molecular properties of Moringa peregrina and Moringa oleifera leaf extracts. Ethanolic and aqueous extracts of both Moringa species were prepared and evaluated against C. auris and other Candida species (Candida spp.) using zone of inhibition (ZI), minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) assays. Phytochemical composition was characterized through fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS) analyses, while cytotoxicity on mammalian MCF-7 cells was assessed using the MTT assay. Molecular docking and 100-ns molecular dynamics simulations were conducted to examine the binding of key bioactive compounds to C. auris dihydrofolate reductase (DHFR; PDB: 8CRH). Ethanolic extracts exhibited the strongest antifungal activity (ZI: 16-16.5 mm; MIC: 0.5-0.7 mg/mL), whereas aqueous extracts were comparatively less effective. FTIR spectra revealed prominent peaks corresponding to hydroxyl (O-H), carbonyl (C = O), and C-O functional groups, confirming the presence of alcohols, esters, phenols, and carboxylic acids, while GC-MS identified β-sitosterol, stigmasterol, dihydroxanthin, and vitamin E derivatives as predominant constituents. Docking results revealed high binding affinities for vitamin E (- 86.6 kcal/mol) and stigmasterol (- 83.5 kcal/mol), exceeding that of fluconazole (- 27.3 kcal/mol). Molecular dynamics confirmed stable protein-ligand complexes, with hydrophobic and van der Waals forces dominating the interactions. Cytotoxicity assays revealed low toxicity at antifungal concentrations (IC₅₀ ≥ 120 µg/mL). These findings demonstrate that Moringa extracts-particularly the ethanolic fractions-harbor potent bioactive compounds with promising antifungal activity against C. auris, highlighting their potential as novel, plant-derived therapeutic candidates to combat resistant fungal infections.