AI Summary & Key Takeaways
AI InsightExperimental validation and structure–activity optimization are warranted to further evaluate their translational and anti-virulence potential.
📌 3 Key Takeaways
Abstract
With increasing antifungal resistance posing a substantial global health challenge, there is an urgent need for novel agents that disrupt core determinants of fungal pathogenicity. Chitin synthase 2 (CHS2), a key enzyme responsible for primary septum formation during cytokinesis, is essential for fungal cell wall integrity, morphogenesis, and survival within the host, yet is absent from mammalian systems making it an attractive, pathogen-selective antifungal target. In this study, we investigated the inhibitory potential of three plant-derived hydroxycinnamic acids ferulic acid, p-coumaric acid, and caffeic acid against C. albicans CHS2 (PDB ID: 7STO) using molecular docking and normal mod analysis (NMA). Docking analyses revealed moderate yet favorable binding affinities, with ferulic acid demonstrating the strongest interaction (−6.7 kcal/mol), followed by caffeic acid (−6.6 kcal/mol) and p-coumaric acid (−6.5 kcal/mol). Normal mode analysis indicated ligand-induced modulation of conformational flexibility, eigenvalues, covariance networks, and elastic properties, consistent with potential stabilization of catalytically inactive conformations that could impair septum formation and hyphal growth, thereby attenuating fungal virulence. These findings support hydroxycinnamic acids as promising natural scaffolds for antifungal lead development targeting chitin biosynthesis and, by extension, key aspects of C. albicans pathogenicity. Experimental validation and structure–activity optimization are warranted to further evaluate their translational and anti-virulence potential.