Repurposing vilanterol as a novel potential antifungal for Candida albicans: In-silico & in-vitro approach

Abstract

Candida albicans infects immune-compromised persons, and its resistance to antifungal drugs has become a significant health concern, which causes a higher mortality rate worldwide. This study aims to find novel antifungals against Candida albicans using a computational drug repurposing approach targeting lanosterol 14-alpha demethylase and experimental testing of the drugs. We used the virtual docking method for initial drug screening. We did minimum inhibitory concentration (MIC), and disc diffusion assay for antifungal determination, and the fungicidal property was detected using the fluorescent microscopy method. Further, we carried out Erg11p drug interaction studies by molecular dynamics simulations and binding free energy analysis. Docking results identified bimatoprost and vilanterol as novel drug hits for C. albicans. In-vitro studies confirmed that vilanterol possesses an active antifungal activity (MIC- 500 µg/ml). The fluorescent microscopy study revealed that vilanterol disrupts the cell membrane of C. albicans at a tested concentration of 600 µg/ml. Molecular dynamics simulations and structural decomposition analysis confirmed the durability of the Erg11p-vilanterol complex's interaction. Our study concludes that vilanterol has a novel potential fungicidal activity against C. albicans. On the other hand, we hypothesize it may alter the ergosterol production by binding lanosterol 14α-demethylase. Previous clinical studies have proved that vilanterol oral doses of up to 500 μg were safe in humans. Our study shows that vilanterol may be a new drug class for treating C. albicans. Therefore, we report that vilanterol could be repurposed possibly against C. albicans infections.

Keywords

• Antifungal
• Candida albicans
• Docking
• Drug-repurposing
• Vilanterol
• Molecular dynamics simulations