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<p>Fungal infections cause nearly 1.7 million deaths each year, with <i>Candida albicans</i> being the leading cause of candidiasis, particularly in patients who are immunocompromised. Fluconazole, a first-line triazole antifungal, is increasingly compromised by resistance mechanisms such as mutations in <i>ERG11</i> gene, efflux pump overexpression, and biofilm formation. This study aimed to identify alternative inhibitors for fluconazole-resistant 14-α-demethylase (Erg11p) through a comprehensive in-silico approach. A pharmacophore-based model was used to screen chemical libraries, followed by molecular docking to evaluate binding affinity, and molecular dynamics simulations to assess complex stability. The lead compound, CHEMBL4110051, exhibited the highest docking score (− 11.3&#xa0;kcal/mol) and stable binding with key catalytic residues. Drug-likeness analysis, safety profiling, and predicted biodegradability further supported its potential. These findings present CHEMBL4110051 as a promising, environmentally conscious alternative to fluconazole for managing <i>C. albicans</i> infections.</p> Graphical abstract <p>Entire workflow to predict the most potent Erg11p inhibitor</p>

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In silico identification of Erg11p blockers as potential inhibitor of clinically isolated azole-resistant Candida albicans

  • 期刊论文

  • 发表日期：

    2026年3月27日

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  • Alipe Saha,
  • Mitrabrata Goswami,
  • Keka Sarkar

摘要

Fungal infections cause nearly 1.7 million deaths each year, with Candida albicans being the leading cause of candidiasis, particularly in patients who are immunocompromised. Fluconazole, a first-line triazole antifungal, is increasingly compromised by resistance mechanisms such as mutations in ERG11 gene, efflux pump overexpression, and biofilm formation. This study aimed to identify alternative inhibitors for fluconazole-resistant 14-α-demethylase (Erg11p) through a comprehensive in-silico approach. A pharmacophore-based model was used to screen chemical libraries, followed by molecular docking to evaluate binding affinity, and molecular dynamics simulations to assess complex stability. The lead compound, CHEMBL4110051, exhibited the highest docking score (− 11.3 kcal/mol) and stable binding with key catalytic residues. Drug-likeness analysis, safety profiling, and predicted biodegradability further supported its potential. These findings present CHEMBL4110051 as a promising, environmentally conscious alternative to fluconazole for managing C. albicans infections.

Graphical abstract

Entire workflow to predict the most potent Erg11p inhibitor