In silico targeting of Candida albicans virulence proteins reveals neem oil phytoconstituents as promising antifungal candidates

Abstract

Candidiasis is a recurrent and clinically significant mycotic infection affecting humans and animals, with increased severity in immunocompromised hosts and growing concerns regarding antifungal resistance. The pathogenicity of Candida albicans is largely mediated by virulence factors such as adhesion proteins and secreted hydrolytic enzymes that facilitate colonization, tissue invasion, and immune evasion. In the present study, an in silico approach was employed to evaluate the antifungal potential of phytoconstituents derived from traditionally used herbal oils by targeting two critical virulence-associated surface proteins of C. albicans, namely Agglutinin-Like Sequence (ALS) and Secreted Aspartyl Proteinase (SAP). Phytoconstituents from neem (Azadirachta indica), garlic (Allium sativum), and tulasi (Ocimum sanctum) oils were selected based on ADMET profiling and compared with the standard antifungal drug ketoconazole. Molecular docking was performed using AutoDock Vina, and ligand-protein interactions were visualized using BIOVIA Discovery Studio Visualizer. Among the tested compounds, neem oil phytoconstituents azadiradione and nimbinene exhibited strong and stable binding affinities toward both ALS and SAP proteins, comparable to ketoconazole. In contrast, garlic-and tulasi-derived phytoconstituents showed relatively weaker interactions with the selected targets. The favorable binding profiles of neem phytoconstituents suggest their potential to interfere with fungal adhesion and proteolytic mechanisms, thereby attenuating C. albicans virulence. Overall, this study highlights neem oil as a promising source of virulence-modulating antifungal candidates and provides a strong computational basis for further in vitro and in vivo validation.