The Potential of Dutasteride for Treating Multidrug-Resistant Candida auris Infection

• Published in: Pharmaceutics Vol. 16; no. 6; p. 810
• Main Authors: Borgio, J Francis, Almandil, Noor B, Selvaraj, Prathas, John, J Sherlin, Alquwaie, Rahaf, AlHasani, Eman, Alhur, Norah F, Aldahhan, Razan, AlJindan, Reem, Almohazey, Dana, Almofty, Sarah, Dhas, T Stalin, AbdulAzeez, Sayed
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-06-2024; MDPI
• Subjects: Antifungal agents; biofilm; Biofilms; Candida auris; Candidiasis; Causes of; Dosage and administration; drug repurposing; Drug resistance; Drug therapy; Drugs; Dutasteride; Epidemics; FDA approval; Health facilities; Infections; Laboratories; Ligands; molecular dynamics simulations; Pathogens; Proteins; Simulation; Testing; virtual screening; Saudi Arabia; United States > US; dutasteride; molecular dynamics simulations; Candida auris; drug repurposing; virtual screening; biofilm; antifungal drugs; planktonic growth; metabolites
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics16060810

Novel antifungal drugs are urgently needed to treat candidiasis caused by the emerging fungal multidrug-resistant pathogen
. In this study, the most cost-effective drug repurposing technology was adopted to identify an appropriate option among the 1615 clinically approved drugs with anti-
activity. High-throughput virtual screening of 1,3-beta-glucanosyltransferase inhibitors was conducted, followed by an analysis of the stability of 1,3-beta-glucanosyltransferase drug complexes and 1,3-beta-glucanosyltransferase-dutasteride metabolite interactions and the confirmation of their activity in biofilm formation and planktonic growth. The analysis identified dutasteride, a drug with no prior antifungal indications, as a potential medication for anti-
activity in seven clinical
isolates from Saudi Arabian patients. Dutasteride was effective at inhibiting biofilm formation by
while also causing a significant reduction in planktonic growth. Dutasteride treatment resulted in disruption of the cell membrane, the lysis of cells, and crushed surfaces on
, and significant (
-value = 0.0057) shrinkage in the length of
was noted at 100,000×. In conclusion, the use of repurposed dutasteride with anti-
.
potential can enable rapid recovery in patients with difficult-to-treat candidiasis caused by
and reduce the transmission of nosocomial infection.