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This research focuses on identifying potential antifungal agents derived from seaweed metabolites to combat Candida auris, a resistant pathogen.

May 22, 2026Open Access

Computational screening of seaweed metabolites as potential antifungal agents against Candida auris

Key Points

This research focuses on identifying potential antifungal agents derived from seaweed metabolites to combat Candida auris, a resistant pathogen.
Screened 1,191 seaweed metabolites using molecular docking to evaluate binding affinities.
Conducted ADMET profiling to refine candidates to three lead compounds: CIDs 145,937, 11,672,129, and 159,086.
Performed molecular dynamics simulations to test the stability of protein-ligand complexes.
CID 145,937 showed the strongest binding free energy of -40.43 kcal/mol, indicating a strong interaction with DHFR.
Lead compounds exhibited favorable drug-likeness and electronic stability through HOMO-LUMO gap analysis.
Molecular dynamics confirmed the stability of the complexes with binding free energies ranging from -48.64 to -70.83 kcal/mol for the leads.

Abstract

Candida auris (C. auris) has emerged as a serious global health threat due to its resistance to antifungal treatments and its persistence in healthcare environments. Effective therapeutic intervention is essential to reduce mortality and transmission. This computational study identifies potential inhibitors of dihydrofolate reductase (DHFR), a crucial enzyme for the survival and replication of C. auris. A total of 1, 191 seaweed metabolites were screened using molecular docking, and the top 20 candidates were selected based on binding affinity. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling further refined the selection to three lead compounds, CIDs 145, 937, 11, 672, 129, and 159, 086, based on their favorable drug-likeness and toxicity profiles. These compounds commonly interacted with active site residues such as GLU₃2, THR₅7, ALA₁1, ILE₉, ILE₁9, LEU₂5, MET₃3, PHE₃6, TYR₁26, and VAL₁0, indicating a shared binding pocket. Post-docking Molecular Mechanics/Generalized Born Surface Area (MM-GBSA) analysis revealed strong protein-ligand interactions, with binding free energies of −40. 43, −54. 74, and −54. 70 kcal/mol, for CIDs 145, 937, 11, 672, 129, and 159, 086, respectively. Highest Occupied Molecular Orbital and Lowest Unoccupied Molecular Orbital (HOMO-LUMO) gap analysis indicated excellent electronic stability, while Prediction of Activity Spectra for Substances (PASS) prediction suggested potential biological activity. Molecular Dynamics Simulation (MD simulation) confirmed the stability of the complex; Principal Component Analysis (PCA) and Dynamic Cross-Correlation Matrix (DCCM) showed consistent dynamics. Post-simulation MM-GBSA binding free energies and PCA3 values were −49. 88, −48. 64, −70. 83 kcal/mol, and 4. 85%, 6. 69%, 8. 25% for CIDs 145, 937, 159, 086, and 11, 672, 129, respectively. In brief, though all leads showed potential against C. auris, CID 145, 937, derived from Ecklonia stolonifera, forms the strongest and most stable complex with the target protein, making it a promising antifungal candidate for further in vitro and in vivo validation. Not applicable.

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