Compound repurposing as an effective antifungal development strategy for the safe production of crops and foods

The infection or contamination of fungi in crops or foods trigger serious food security and safety concern worldwide. Long-term application of conventional antifungal agents, such as azole, strobilurin or fludioxonil fungicides, during crop/food production can result in the emergence of fungicide-resistant fungi, for which effective agents for treating resistant fungal pathogens or contaminants are often very limited. Since the development of entirely new antifungal agents is an expensive and time-consuming process, we investigated an innovative approach termed "compound repurposing", which repositioned already marketed non-antifungal compounds as new antifungal agents for the control of fungal infections/contaminations. We also employed a "chemo-sensitization" strategy wherein co-application of potentiators (chemo-sensitizers), for example, redox-modulatory molecules, could enhance the antifungal efficacy of the screened compounds. We found that compounds such as polyphenol, terpenoid or medicinal agents, which have been used as nutrient supplements, non-antifungal medicines, etc., exerted potent antifungal activity against crop/food fungal pathogens or contaminants including Aspergillus sp. and Fusarium sp. Repurposed compounds also inhibited the biosynthesis of aflatoxins by Aspergillus flavus or Aspergillus parasiticus, thus ensuring safe production of crops/foods. Collectively, antifungal "compound repurposing" could serve as a promising strategy that can identify new crop/food protection molecules; "chemo-sensitization" significantly improved the antifungal efficacy of the screened compounds.