Identification of novel drug targets and screening potential drugs against Cryptococcus gattii: An in silico approach

Abstract

Cryptococcus gattii is an emerging fungal pathogen responsible for causing cryptococcosis, which is an infectious disease with a global prevalence and a wide range of clinical manifestations. C. gattii can enter the host's brain and harm human peripheral blood mononuclear cells' DNA. It is vital to investigate potential alternative medications to treat this disease since global antifungal resistance is on the rise. Concerning the current situation, an in-silico approach was conducted to find novel therapeutics. Among 6561 proteins of C. gattii three druggable proteins (XP 003194316.1, XP 003197297.1, XP 003197520.1) were found after completing a series of steps including the exclusion of paralogs, human homologs, non-essential and human microbiome homologs proteins. These proteins were involved in unique pathogen pathways; thus, they can be utilized as potential therapeutic targets without causing any harm to humans. The subcellular locations and their interactions with a high number of proteins also demonstrate their eligibility as putative drug targets. These proteins were docked with 21 potential antifungal plant metabolites. Molecular docking analysis revealed that amentoflavone, baicalin, rutin and viniferin could be the most effective drug candidates because of the highest binding affinity. Among these drug candidates, XP 003197520.1 with amentoflavone showed the lowest docking score of −253. These protein-ligand complexes were also analyzed to be stable during molecular dynamic simulation. Correspondingly, the drugs showed proper ADME properties and were also analyzed to be safe. These potential drugs could be effective to treat Cryptococcosis. In-vivo trial is highly recommended for further prospects.