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Antifungal Drug Discovery: Progresses, Challenges, Opportunities, 2nd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pharmacology".

Deadline for manuscript submissions: 20 December 2025 | Viewed by 1155

Special Issue Editor

Special Issue Information

Dear Colleagues,

The arsenal of antifungal drugs for the treatment of human mycoses is confined to a few compound classes such as azoles, echinocandines, and polyenes, while the eminent health risks based on fungal infections are continuously rising. Immunocompromised people (e.g., elderly people, organ transplantation and cancer patients, and persons infected with HIV) especially suffer from life-threatening systemic fungal infections. The formation of drug-resistant pathogenic fungal strains, as well as the emergence of new highly problematic species such as Candida auris, pose a considerable global threat, warranting the development of new and efficient antifungal drug candidates with limited side effects. The severe skin mycoses eumycetoma, chromoblastomycosis, and sporotrichosis are classified as neglected tropical diseases (NTDs), with potent antifungals still needing to be discovered and existing drugs being inefficient and often unavailable for patients in rural tropical and subtropical regions.

Thus, new fungicidals with enhanced activity, reduced side effects, and the ability to circumvent drug resistance mechanisms are sought. Promising strategies include the optimization of existing antifungals and the development of first-generation inhibitors of new fungal drug targets. In this regard, the identification and validation of suitable new targets and mechanisms is of high relevance, and these can also include vital interactions of the fungal pathogen with the host. Straightforward formulation and conjugate systems can improve pharmacokinetics and targeting properties. The repurposing of known drugs against other ailments and the rapid and cost-effective application of few-step chemical procedures and multi-component reactions can quickly lead to useful hit compounds.

This Special Issue covers the latest developments and the state-of-the-art of drug design and discovery for the treatment of fungal infections. Original research articles, review articles, perspectives, and short communications including (but not restricted to) the described research fields are welcome.

Dr. Bernhard Biersack
Guest Editor

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Keywords

  • antifungal drugs
  • fungal infections
  • drug design
  • drug discovery
  • targeted therapy
  • drug resistance
  • fungal drug targets
  • neglected tropical diseases

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Published Papers (2 papers)

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Research

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11 pages, 240 KB  
Article
Beneficial Effect of Olive Leaf Extract as an Adjunct to Standard Antifungal Therapy in Treating Candida-Related Oral Diseases
by Maja Kinkela Devčić, Irena Glažar, Igor Pasković, Daniela Kovačević-Pavičić, Josip Peradinovic, Ivana Munitic and Sunčana Simonić-Kocijan
Int. J. Mol. Sci. 2025, 26(17), 8193; https://doi.org/10.3390/ijms26178193 - 23 Aug 2025
Viewed by 388
Abstract
The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and [...] Read more.
The aim of this study was to evaluate whether combined administration of olive leaf extract (OLE) with standard antifungal therapy—nystatin (NYS) or miconazole (MIC) could be a more efficient alternative in reducing the number of Candida colonies, the presence of oral signs and symptoms and changes in salivary IL-17A level compared to standard therapy alone. The study included 59 subjects with a positive microbiological Candida colony number greater than 600 CFU/mL and at least one oral sign or symptom present. Subjects were randomly divided into four groups depending on applied therapy: OLE + NYS group (n = 15), OLE + MIC group (n = 15), NYS group (n = 14), MIC group (n = 15). Therapy duration and clinical monitoring were standardized across all groups. There was no significant difference between the tested groups in Candida spp. colony number or salivary IL-17A levels. In the OLE + NYS group, a significant increase in salivation rate was observed, while a significant decrease in tongue burning was reported in the OLE + MIC group. A significant reduction in burning of the oral mucosa and tongue was observed in the MIC group. No significant differences were found in other clinical signs or symptoms among treatment groups. OLE, as an adjunct to standard antifungal therapy, did not significantly reduce Candida spp. colony number or salivary IL-17A levels. However, in combination with NYS it increased salivation rate, while in combination with miconazole, it significantly decreased tongue burning. Both symptoms are common clinical findings in oral Candida-related disease and suggest that OLE may have supportive potential in the clinical management of these conditions. Further research is needed to explore its potential therapeutic benefits on oral health. Full article

Review

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33 pages, 1549 KB  
Review
Exploring a Therapeutic Gold Mine: The Antifungal Potential of the Gold-Based Antirheumatic Drug Auranofin
by Jingyi Ma, Wendy van de Sande and Bernhard Biersack
Int. J. Mol. Sci. 2025, 26(16), 7909; https://doi.org/10.3390/ijms26167909 - 16 Aug 2025
Viewed by 335
Abstract
Human fungal infections comprise systemic mycoses as well as various skin diseases. Rising case numbers along with inefficient therapies and the appearance of drug-resistant strains unleashed a considerable health problem over the last years. Thus, the identification and development of new antifungal drugs [...] Read more.
Human fungal infections comprise systemic mycoses as well as various skin diseases. Rising case numbers along with inefficient therapies and the appearance of drug-resistant strains unleashed a considerable health problem over the last years. Thus, the identification and development of new antifungal drugs is mandatory, which can include the design of new antifungals, or, more time saving, the repurposing of known drugs already applied for the therapy of other human diseases. The orally applicable gold-based drug auranofin has been used for the treatment of rheumatoid arthritis since the 1980s. However, auranofin also showed marked activity against various cancers, microbes, parasites, and viruses. Facing a pressing need to find new drug candidates against mycoses, especially against those listed in the WHO fungal pathogen priority list, we have summarized the eminent antifungal activities of auranofin in this review. Given its established safety profile and broad-spectrum activity, auranofin represents a promising candidate for repurposing in antifungal therapy. The mechanism of action of auranofin was correlated with thioredoxin reductase inhibition, but other modes of action such as interference with mitochondrial protein import and NADH kinase were also described and discussed. A selection of promising antifungal gold complexes was also provided. Pertinent literature is covered until 2025. Full article
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