Repurposing of Ribavirin as an Adjunct Therapy against Invasive Strains in an Study.

The use of antifungal agents in clinical settings is limited by the appearance of drug resistance and adverse side effects. There is, therefore, an urgent need to develop new drugs to strengthen the treatment of invasive fungal diseases. The aim of this study is to describe the potential repurposing of ribavirin as an adjunct therapy against spp. Primary screening of a Prestwick Chemical library against ATCC 90028 and fluconazole-resistant strains was performed. Subsequently, we evaluated the responses of 100 sp. strains to ribavirin, an antiviral agent, using the broth microdilution method as recommended by CLSI. We checked the involvement of efflux pump activity in the development of ribavirin resistance. We studied time-kill curves and performed a checkerboard assay for a ribavirin-antifungal combination study. Twenty-one nonstandard antifungal compounds were identified, including ribavirin. Ribavirin had antifungal activity against 63 strains, including strains of , , and , with MICs ranging from 0.37 to 3.02 μg/ml, while MICs for , , , and some strains remained high (≥24.16 μg/ml). No relation was observed between efflux pump activity and ribavirin resistance. Ribavirin exhibited fungistatic activity against multidrug-resistant (MDR) and fungicidal activity against a strain. In addition, ribavirin acted synergistically with azoles against strains for which ribavirin MICs were <24.4 μg/ml. This study highlights the potential clinical application of ribavirin, alone or in association with other antifungal agents, as an adjunct anti- drug.