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Revolutionizing Antifungal Therapeutics: From Understanding to Intervention
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Revolutionizing Antifungal Therapeutics: From Understanding to Intervention

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

Deadline for manuscript submissions: closed (20 August 2025) | Viewed by 1574

Special Issue Editor

Dr. Célia Fortuna Rodrigues

E-Mail Website
Guest Editor
1. Associate Laboratory i4HB—Institute for Health and Bioeconomy, University Institute of Health Sciences—CESPU, 4585-116 Gandra, Portugal
2. ALiCE—Associate Laboratory in Chemical Engineering, Faculty of Engineering, LEPABE—Laboratory for Process Engineering, Environment, Biotechnology and Energy, Faculty of Engineering, University of Porto, Porto, Portugal
Interests: biofilms; Candida; AMR; fungal infection; polymicrobial biofilms; alternatives to antifungals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal infections are a worldwide threat, carrying not only high morbidity and mortality rates but also high healthcare costs. It has been anticipated that 10 million people die per year from infections related to multidrug-resistant pathogens, of which several include fungal species. A high percentage of the mortalities caused by fungi are known to be biofilm-related.

This Special Issue is intended to cover the state of antifungal research, comprising new compounds with antifungal activity. We welcome reviews and original research articles covering the development/evaluation/validation of recent studies, especially those regarding multidrug resistance.

Dr. Célia Fortuna Rodrigues
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fungi
  • antifungal
  • biofilm
  • Candida
  • Aspergillus
  • Trichoderma

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Published Papers (2 papers)

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Research

21 pages, 6211 KiB  
Article
In Silico and In Vitro Potential Antifungal Insights of Insect-Derived Peptides in the Management of Candida sp. Infections
by Catarina Sousa, Alaka Sahoo, Shasank Sekhar Swain, Payal Gupta, Francisco Silva, Andreia S. Azevedo and Célia Fortuna Rodrigues
Int. J. Mol. Sci. 2025, 26(15), 7449; https://doi.org/10.3390/ijms26157449 - 1 Aug 2025
Viewed by 399
Abstract
The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the [...] Read more.
The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article
(This article belongs to the Special Issue Revolutionizing Antifungal Therapeutics: From Understanding to Intervention)
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16 pages, 2096 KiB  
Article
Acridine Derivatives as Antifungal and Antivirulence Agents Against Candida albicans
by Amra Yunus, Oluwatosin Oluwaseun Faleye, Jin-Hyung Lee and Jintae Lee
Int. J. Mol. Sci. 2025, 26(15), 7228; https://doi.org/10.3390/ijms26157228 - 25 Jul 2025
Viewed by 552
Abstract
Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal [...] Read more.
Candida albicans is a clinically important fungal pathogen capable of causing both superficial and systemic infections, particularly in immunocompromised individuals. A key factor contributing to its pathogenicity is its ability to form biofilms, structured microbial communities that confer significant resistance to conventional antifungal therapies. Addressing this challenge, we explored the antivirulence potential of acridine derivatives, a class of heterocyclic aromatic compounds known for their diverse biological activities, including antimicrobial, antitumor, and antiparasitic properties. In this study, a series of acridine derivatives was screened against C. albicans biofilms, revealing notable inhibitory activity and highlighting their potential as scaffolds for the development of novel antifungal agents. Among the tested compounds, acridine-4-carboxylic acid demonstrated the most promising activity, significantly inhibiting the biofilm formation at 10 µg/mL without affecting planktonic cell growth, and with a minimum inhibitory concentration (MIC) of 60 µg/mL. Furthermore, it attenuated filamentation and cell aggregation in a fluconazole-resistant C. albicans strain. Toxicity assessments using Caenorhabditis elegans and plant models supported its low-toxicity profile. These findings highlight the potential of acridine-based scaffolds, particularly acridine-4-carboxylic acid, as lead structures for the development of therapeutics targeting both fungal growth and biofilm formation in Candida albicans infections. Full article
(This article belongs to the Special Issue Revolutionizing Antifungal Therapeutics: From Understanding to Intervention)
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