Drug Repurposing to Fight Resistant Fungal Species: Recent Developments as Novel Therapeutic Strategies

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Background

Every year the incidence of life-threatening fungal diseases increases, leading to over 1.5 million deaths annually. The rapidly rising burden of disease is further compounded by the emergence of drug-resistant and/or multidrug-resistant strains. People most at risk are those with immunodeficiency disorders, who have undergone transplant surgery, chemoradiotherapy, or treatment with immunosuppressive agents. The current antifungal therapeutics pose critical challenges to clinicians, as there is a limited number of antifungals, a high rate of resistance, drug-induced toxicity, poor pharmacokinetic profiles, and dangerous drug-drug interactions. These factors prompted the WHO to urge researchers to develop innovative antifungal agents with no cross-resistance to existing antifungal classes and with new modes of action. Several agents have recently been confirmed to serve as antifungal candidates in the treatment of mycoses.

Compared with the development of new drugs, drug repurposing offers several advantages, primarily in terms of reduced cost and security risk. This practice involves tapping into new applications for existing drugs, necessitating detailed clinical investigation into pharmacological mechanisms. Implementing drug repurposing strategies serves as a groundbreaking approach to the identification of new antifungal drugs through structural readjustment.
Due to the existence of toxicity and drug-resistant strains, the present antifungal options have become increasingly restricted. To address this, a variety of strategies have been implemented for antifungal therapy. These strategies include developing new synthetic drugs, utilizing extracts from organisms, modifying the administration methods or forms of existing drugs to combat fungal diseases, and exploring the combination of known antifungal and non-antifungal agents.

Antifungal agents, with idealized properties like: a) highly selective for fungal targets, b) good pharmacokinetics, c) suitable for both oral, intravenous, and/or inhaled formulations, and d) fungicidal rather than fungistatic attracted attention. Surprisingly, drug repurposing is a potential strategy for the treatment of invasive fungal infections, owing to the excellent antifungal activity of these drugs to prevent further antifungal resistance, enhance efficacy, and minimize toxicity. Rising to the global call, this Research Topic will progress repurposing drugs and an informed development strategy to enhance efficacy, appropriate antifungal activity against fungal species, and mitigate resistance.

We welcome submissions focusing the the following subtopics:
1. Identification of Potential Candidates:
• Investigation of existing drugs with potential antifungal properties(MIC and MFC determination).
2. Mechanisms of Antifungal Activity:
• Investigation into the specific mechanisms through which repurposed drugs exhibit antifungal effects.
• Understanding the interaction between repurposed drugs and fungal pathogens.
3. Optimization of Drug Formulations:
• Research on optimizing drug formulations for enhanced antifungal efficacy.
4. Synergistic Effects and Combination Therapies:
• Study of potential synergies between repurposed drugs and existing antifungal agents.
5. Drug resistance and Efficacy:
• Assessing the potential effect for inhibition of drug-resistant genes in fungal species
• Exploring the long-term efficacy and sustainability of repurposed drugs as antifungal agents.
• Anti-Biofilm activity: Evaluation of repurposing drugs on Biofilm formation against fungal species(yeast and filamentous agents ).

Keywords: drug resistance, novel antifungal agents, repurposing, therapeutic option

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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