|Kim, Jong Heon|
|Chan, Kathleen - Kathy|
|SHILMAN, MIKHAIL - Keck Graduate Institute|
|LAND, KIRKWOOD - Pacific University|
Submitted to: Antibiotics
Publication Type: Review Article
Publication Acceptance Date: 11/13/2020
Publication Date: 11/15/2020
Citation: Kim, J., Cheng, L.W., Chan, K.L., Tam, C.C., Mahoney, N.E., Friedman, M., Shilman, M.M., Land, K.M. 2020. Antifungal drug repurposing. Antibiotics. 9(11):812. https://doi.org/10.3390/antibiotics9110812.
Interpretive Summary: There have been persistent efforts to improve the efficacy of conventional antifungal drugs or intervention strategies. However, the development of entirely new antifungal drugs is a very expensive and time-consuming process. It is estimated that the overall timelines and costs from the new antifungal lead discovery to regulatory approval, especially for those overcoming drug-resistant fungal pathogens, takes more than 10 years and > $300 million, respectively, excluding the $400 million for marketing efforts over the lifespan of a product. Recently, there have been alternative approaches termed antifungal drug repurposing by which new utility of various types of marketed, non-antifungal drugs are repositioned as novel antifungal agents. Here we discuss the current needs for the development of new antifungal interventions, and comment on the recent antifungal drug repurposing efforts as the alternative approaches for fungal pathogen control.
Technical Abstract: Control of fungal pathogens is increasingly problematic due to the limited number of effective drugs available for antifungal therapy. Conventional antifungal drugs also trigger serious human cytotoxicity associated with kidneys and liver, including the generation of reactive oxygen species. Moreover, the increased incidences of fungal resistance to a class of azoles, echinocandins, etc., make this problem a global human health issue. Of note, certain azole fungicides such as propiconazole or tebuconazole that are applied to the agricultural fields have the same mechanism of antifungal action as clinical azole drugs. Such long-term application of azole fungicides to crop fields provides environmental selection pressure for the emergence of pan-azole-resistant fungal strains such as the Aspergillus fumigatus TR34/L98H mutant, a causative agent of human invasive aspergillosis. Altogether, emerging resistance of pathogens to currently available antifungal drugs and an insufficiency in discovery of new therapeutics engender the urgent need for the development of new antifungals and/or alternative therapies for effective control of fungal pathogens. In this communication, we discussed the current needs of the discovery of new clinical antifungal drugs and the recent drug repurposing endeavors as the alternative methods for fungal pathogen control.