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Background <p><i>Candida auris (C. auris)</i> 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 <i>C. auris</i>.</p> Result <p>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 GLU_32, THR_57, ALA_11, ILE_9, ILE_19, LEU_25, MET_33, PHE_36, TYR_126, and VAL_10, 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.</p> Conclusion <p>In brief, though all leads showed potential against <i>C. auris</i>, CID 145,937, derived from <i>Ecklonia stolonifera</i>, 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.</p> Clinical trial number <p>Not applicable.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月20日

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  • Md. Al-Amin,
  • Afsana Mustak Mim,
  • Salman Reja,
  • Samia Sadaf,
  • Md. Younus Shekh,
  • Sabiha Akter,
  • Ive Sithi Chambugong,
  • Shanjida Akter Joyoti,
  • Md. Ifteker Hossain,
  • Noimul Hasan Siddiquee

摘要

Background

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.

Result

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 GLU_32, THR_57, ALA_11, ILE_9, ILE_19, LEU_25, MET_33, PHE_36, TYR_126, and VAL_10, 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.

Conclusion

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.

Clinical trial number

Not applicable.