Projecting phytochemical bacoside A anti-mucorale agent: An in-silico and in-vitro assessment

Abstract

Mucormycosis, a life-threatening fungal infection that primarily affects immunocompromised individuals.The protein family commonly observed in the fugus responsible for causing Mucormycosis. The attachment of spores to host cells surface, facilitated by a protein CotH, is a critical step for the invasion and progression of the disease. Therefore, CotH inhibitors have emerged as a promising therapeutic strategy for treating mucormycosis.This study presents a novel therapeutic target and ligand for controlling the growth of Mucorales. First, to identify potential CotH inhibitors, we surveyed a library antifungal compounds elaborated in AYUSearch database. Next, using machine learning-based algorithms we screend 20 potentials ligands, followed by structure-based molecular modelling and molecular trajectory analysis to identify the three most promising chemical constituents. In-vitro tube assays on selected Mucorales determined the minimum inhibitory concentrations (MIC) for screened chemotypes. The MIC assay revealed that Bacoside inhibits the growth and sporulation at 5 mg/ml concentrations, emerging as a probable CotH inhibitor. Further, the compound's toxicity was evaluated by adding it to the feed of C.elegans, and the finding suggests that the bacoside is reasonably safe at the studied concentration. The findings project bacoside A as a potential anti-mucorale lead compound that can be further validated with preclinical and clinical studies.

Keywords

• Bacoside
• C.elegans
• CotH
• Machine learning
• Mucormycosis