Análise in vitro e in silico do potencial anti-candida Albicans do peptídeo sintético Temporina-Sha

Abstract

The emergence of Candida albicans strains resistant to conventional antifungal agents, particularly fluconazole, has driven the search for new therapeutic strategies, among which antimicrobial peptides stand out. In this study, the antifungal potential of Temporin-SHa was evaluated against clinical C. albicans isolates, including fluconazole-resistant strains, and its possible mechanisms of action were investigated using experimental and computational approaches. Antifungal activity assays demonstrated a minimum inhibitory and fungicidal concentration for TSHa of 7.81-31.25 µg/mL and reduced fungal growth at subinhibitory concentrations. The assessment of virulence factors showed that TSHa did not significantly interfere with phospholipase activity. However, it exhibited relevant inhibition of proteinase and hemolytic activities, with performance comparable to or superior to that of fluconazole. Molecular docking analyses, performed using three-dimensional protein structures predicted by AlphaFold, indicated stable interactions between T-SHa and protein encoded by the CYP51 gene, with higher affinity toward the CYP51 target, suggesting a multifactorial mechanism of action involving both fungal membrane integrity and modulation of virulence factors. Predictive ADMET analysis revealed limitations for oral administration, which are common to antimicrobial peptides, but indicated favorable characteristics for topical or parenteral applications. Overall, the results demonstrate that TSHa is a promising Candidate for developing new antifungal strategies, while highlighting the need for further studies to validate its efficacy, safety, and therapeutic applicability.