Repurposing Benzbromarone as Antifolate to Develop Novel Antifungal Therapy for Candida Albicans

Abstract Fungal infections in humans are responsible for mild to severe infections resulting in the systemic effects responsible for a large amount of mortality. The invasive fungal infections are having similar symptomatic effects to those of COVID-19. The COVID-19 patients are immunocompromised in nature and have a high probability of developing severe fungal infections resulting in the development of further complications. The existing antifungal therapy is having associated problems related to the development of drug resistance, sub-potent in nature, and the presence of undesirable toxic effects. The fungal dihydrofolate reductase is an essential enzyme involved in the absorption of dietary folic acid and its conversion into tetrahydrofolate, which is a coenzyme required for the biosynthesis of the fungal nucleotides. Thus, in the current study, an attempt has been made to identify potential folate inhibitors of Candida albicans by a computational drug repurposing approach. Benzbromarone is identified as a potential anti-folate agent based upon the molecular docking simulation-based virtual screening followed by the molecular dynamic simulation of the macromolecular complex for the development of a novel therapy for the treatment of candidiasis.