Antifungal potential of marine bacterial compounds in inhibiting Yck2 to overcome echinocandin resistance: a molecular dynamics study.

(), a common fungal pathogen, poses a significant threat to immunocompromised individuals, particularly due to the emergence of resistance against echinocandins, a primary class of antifungal agents. Yck2 protein, a key regulator of cell wall integrity and signaling pathways in was targeted to overcome this resistance. A virtual screening was used to identify Yck2 inhibitors from marine bacterial compounds. Further re-docking, molecular dynamics simulations, and various analyses such as root mean square deviation (RMSD), root mean square fluctuation (RMSF), hydrogen bonding, free binding energy calculations, and RG-RMSD-based free energy landscape were conducted to evaluate the efficacy and stability of the identified compounds. Among the compounds screened, CMNPD27166 and CMNPD27283 emerged as the most promising candidates, demonstrating superior binding affinities, enhanced stability, and favorable interaction dynamics with Yck2, surpassing both the control and other compounds in efficacy. In contrast, CMNPD19660 and CMNPD24402, while effective, showed lesser potential. These findings highlight the utility of computational drug discovery techniques in identifying and optimizing potential therapeutic agents and suggest that marine-derived molecules could significantly impact the development of novel antifungal therapies. Further experimental validation of the leading candidates, CMNPD27166 and CMNPD27283, is recommended to confirm their potential as effective antifungal agents against echinocandin-resistant infections.