Targeting calcineurin to combat fungal infections: Computational insights into phytochemicals as promising antifungal agents

Background Although both fungi and bacteria are considered the primary causes of dermatological diseases, Aspergillus fumigatus , Candida albicans , and Cryptococcus neoformans are the predominant pathogens responsible for such conditions globally. Therefore, the present study aimed to identify a novel phytochemical that inhibits calcineurin. Methods In this study, Schrödinger's Maestro V.13.8 software was employed for Induced Fit Docking (IFD), while its Desmond module was used to perform molecular dynamics simulations. Results In molecular docking, amaroswerin had a docking score of −9.0121 kcal/mol and IFD score of 672.34 kcal/mol. However, the co-crystal ligand FK-506 exhibited a docking score of −8.217 kcal/mol. Moreover, the interaction map showed that amaroswerin has a strong binding affinity for the target, as evidenced by six hydrogen bond contacts and a π–π stacking contact. In the assessment of binding stability, the c-α atoms of the amaroswerin-calcineurin complex demonstrated a root mean square deviation (RMSD) of less than 2.8 Å over a 500 ns period implying that the complex has good binding stability. The post-MD interaction plot revealed that amaroswerin exhibited more robust interactions with calcineurin, with binding percentages ranging from 54 to 99 %. Furthermore, amaroswerin was not associated with oral toxicity, acute eye corrosion or irritation, or acute skin sensitization, with confidence levels of 60 %, 60 %, and 70 %, respectively. Conclusion The present study concludes that amaroswerin could be a promising candidate for the development of antifungal agents.