Development and research progress of anti-drug resistant fungal drugs

Cui, Xiangyi; Wang, Lanlin; Lü, Yuhong; Yue, Changwu

doi:10.1016/j.jiph.2022.08.004

Cited by 85Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal Infections and Studies

Development and research progress of anti-drug resistant fungal drugs

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Cui, Xiangyi, Wang, Lanlin, Lü, Yuhong, Yue, Changwu·2022·Journal of Infection and Public Health

DOI 10.1016/j.jiph.2022.08.004

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Abstract

With the widespread use of immunosuppressive agents and the increase in patients with severe infections, the incidence of fungal infections worldwide has increased year by year. The fungal pathogens Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus cause a total of more than 1 million deaths each year. Long-term use of antifungal drugs can easily lead to fungal resistance, and the prevalence of drug-resistant fungi is a major global health challenge. In order to effectively control global fungal infections, there is an urgent need for new drugs that can exert effective antifungal activity and overcome drug resistance. We must promote the discovery of new antifungal targets and drugs, and find effective ways to control drug-resistant fungi through different ways, so as to reduce the threat of drug-resistant fungi to human life, health and safety. In the past few years, certain progress has been made in the research and development of antifungal drugs. In addition to summarizing some of the antifungal drugs currently approved by the FDA, this review also focuses on potential antifungal drugs, the repositioned drugs, and drugs that can treat drug-resistant bacteria and fungal infections, and provide new ideas for the development of antifungal drugs in the future.

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Drug repurposing leverages agents with well-established safety and efficacy profiles to shorten development timelines and reduce costs.
“Within this context, drug repurposing has emerged as a compelling and pragmatic strategy, leveraging agents with well‐established safety and efficacy profiles to shorten development timelines and reduce costs [16].”
From Statins as Antifungal Agents: A Review on Drug Repurposing and Nanotechnology-Driven Delivery Strategies (2025) · cites this paper as [16]
Section 3.3, “Drug repurposing” (page unavailable), says repositioning uses drugs already approved or in clinical trials and can significantly reduce the time, effort, and money needed to develop antifungal treatments. It does not say that all such agents have well-established safety and efficacy profiles; drugs still in trials may not. (LLM, conf=0.86)
Experimental — accuracy not yet measured
Long-term regimen courses and overuse of azoles, polyene, and echinomycin have led to the high prevalence of drug resistance.
“Long-term regimen courses and overuse of azoles, polyene, and echinomycin have led to the high prevalence of drug resistance (3).”
From Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review (2023) · cites this paper as [3]
Existing antifungals have limitations such as toxic side effects, narrow-range antifungal spectra, and antifungal resistance.
“Although existing antifungals are widely applied in the clinical setting, they still have many limitations, such as toxic side effects, narrow-range antifungal spectra, and antifungal resistance.”
From Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review (2023) · cites this paper as [3]

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Gupta, A. K., Venkataraman, M., Shear, N. H., & Piguet, V. (2020) · Dermatologic Therapy · doi:10.1111/dth.13613 · Cited by 6 · see citing works
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Xiaoyan H, Yali S, Bai Pu e a. System classification of antifungal drugs, resistance mechanisms and development of new drugs. [J] China Mod Appl Pharm 2019;36:1430-6.
SCYNEXIS Announces Positive Top-Line Results from its Second Pivotal Phase 3 Study (VANISH-306) of Oral Ibrexafungerp for the Treatment of Vulvovaginal Candidiasis (Vaginal Yeast Infection) , < 〈https://www.scynexis.com/news-media/ press-releases/detail/207/scynexis-announces-positive-top-line-results-from- its〉 > (.
CIDARA THERAPEUTICS ANNOUNCES NEW DATA FOR REZAFUNGIN AT THE 21ST ICHS SYMPOSIUM, < 〈http://ir.cidara.com/news-releases/news-release-details/ cidara-therapeutics-announces-new-data-rezafungin-21st-ichs〉 > (.

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Antifungals: From Pharmacokinetics to Clinical Practice
do Carmo, A., Rocha, M. J., Pereirinha, P., Tomé, R., & Costa, E. (2023) · Antibiotics · doi:10.3390/antibiotics12050884 · Cited by 112 · see citing works
Potential Strategies to Control the Risk of Antifungal Resistance in Humans: A Comprehensive Review
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Antifungal Activity of Mycogenic Silver Nanoparticles on Clinical Yeasts and Phytopathogens
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Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review
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Nanoparticle-based antifungal therapies innovations mechanisms and future prospects
Wu, Q., Cen, F., Xie, Y., Ning, X., Wang, J., Lin, Z., & Huang, J. (2025) · PeerJ · doi:10.7717/peerj.19199 · Cited by 34 · see citing works
Anti-Malassezia Drug Candidates Based on Virulence Factors of Malassezia-Associated Diseases
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Deep Learning Combined with Quantitative Structure‒Activity Relationship Accelerates De Novo Design of Antifungal Peptides
Yin, K., Li, R., Zhang, S., Sun, Y., Huang, L., Jiang, M., Xu, D., & Xu, W. (2025) · Advanced Science · doi:10.1002/advs.202412488 · Cited by 28 · see citing works
Nucleoside analogues: N-glycosylation methodologies, synthesis of antiviral and antitumor drugs and potential against drug-resistant bacteria and Alzheimer's disease
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Medical Applications of Silver and Gold Nanoparticles and Core‐Shell Nanostructures Based on Silver or Gold Core: Recent Progress and Innovations
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Novel Strategies for Preventing Fungal Infections—Outline
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Garlic-Derived Quorum Sensing Inhibitors: A Novel Strategy Against Fungal Resistance
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Fungi and mycotoxin types, toxicity, mechanisms, and control of mycotoxin contamination: a review
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Anacardiaceae Family: Effect of Isolated Compounds and Other Identified Phytochemicals Against Clinically Relevant Candida Species—A Short Review
Guerra, R. N. M., Oliveira, A. D. S., Farias, J. R., Franco, D. C. G., Santos, P. G., Barbosa, N. T., Muniz, S. B., Abreu, A. G., & do Nascimento, F. R. F. (2025) · Antibiotics · doi:10.3390/antibiotics14030308 · Cited by 9 · see citing works
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“Within this context, drug repurposing has emerged as a compelling and pragmatic strategy, leveraging agents with well-established safety and efficacy profiles to shorten development timelines and reduce costs [16].”
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Baicalin promotes β-1,3-glucan exposure in Candida albicans and enhances macrophage response
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Roles of alcohol dehydrogenase 1 in the biological activities of Candida albicans
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Analysis of rhizosphere soil microbial diversity and its functions between Dahongpao mother tree and cutting Dahongpao
Jia, X., Li, M., Zhang, Q., Jia, M., Lei, H., Zhang, S., Wang, Y., Luo, Y., Wang, T., Ye, J., et al. (2024) · Frontiers in Plant Science · doi:10.3389/fpls.2024.1444436 · Cited by 5 · see citing works
Synergism Between Essential Oils and Evaluation of Their Activities with a Focus on Malassezia furfur Control
Cassola, F., Ramírez, N., Ribeiro, G., da Silva, L. H. D., Gambero, A., de Oliveira, A. D. S. S., Moraes‐Vieira, P. M., Resende, F. A., & Duarte, M. C. T. (2023) · Planta Medica · doi:10.1055/a-2196-2087 · Cited by 5 · see citing works
Anti‐Candida Phytochemicals and Isolated Compounds in Anacardiaceae Family—An Updated Review and In‐Silico AnalysisPreprint
Oliveira, A. D. S., Farias, J. R., Franco, D. C. G., da Costa, A. A. C., Santos, P. G., Silva, M. C. P. D., do Nascimento, F. R. F., & Guerra, R. N. M. (2024) · Preprints.org · doi:10.20944/preprints202404.1065.v1 · Cited by 4 · see citing works
A computational approach to identify novel plant metabolites against Aspergillus fumigatus
Ahmed, J., Raihan, M. M., Robin, T. B., Sami, M. R. S., Mahfuz, S., Haque, N., Akter, H., Bappy, M. N. I., Afrin, D., & Moli, M. A. (2023) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2023.101385 · Cited by 4 · see citing works
Design and Synthesis of Novel Amino and Acetamidoaurones with Antimicrobial Activities
Maio, A. D., Olleik, H., Courvoisier‐Dezord, E., Guillier, S., Neulat-Ripoll, F., Haudecoeur, R., Bolla, J., Casanova, M., Cavalier, J., Canaan, S., et al. (2024) · Antibiotics · doi:10.3390/antibiotics13040300 · Cited by 4 · see citing works
Effects of Nisin A Combined with Antifungal Drug Against Growth of Candida Species
Niitani, Y., Ohta, K., Yano, K., Kaneyasu, Y., Maehara, T., Kitasaki, H., Shigeishi, H., Nishi, H., Nishimura, R., Naito, M., et al. (2025) · Dentistry Journal · doi:10.3390/dj13040160 · Cited by 4 · see citing works
Exploring SAR and Antifungal Activity of Pyrazole‐Thiazole‐Hydrazone Compounds Through Synthesis and Docking Studies
Halimi, G., Osmani̇ye, D., Sağlık, B. N., Levent, S., Özkay, Y., & Kaplancıklı, Z. A. (2025) · Chemistry & Biodiversity · doi:10.1002/cbdv.202501313 · Cited by 3 · see citing works
Synthesis, antimicrobial activity and in-silico studies of (1-(1-arylethyl)-1H-1,2,3-triazolyl-2-phenylquinoline-4-carboxylate derivatives with click chemistry
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Unveiling antimicrobial potential of thiazolyl-1,2,3-triazolyl-ethanol derivatives: Synthesis and molecular docking studies
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Biomolecular Insights Into the Antifungal Activity of Allium Species Constituents: From Mechanisms to Applications
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Bibliometric Assessment of the Global Research Trends in Antimicrobial Resistance for Fungal Species
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The conserved protein DopA is required for growth, drug tolerance and virulence in Aspergillus fumigatus
Wei, Q., He, C., Peng, X., An, B.-K., Peng, M., Wang, X., Zhang, C., Lü, L., Sang, H., & Kong, Q. (2024) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-024-04234-1 · Cited by 3 · see citing works
Reversibly Cross-Linked Asymmetric Hybrid Open-Polysilsesquioxane Films Enhancing Clotrimazole Bioavailability and Anti-Candida Mature Biofilm Activity for Vaginal Therapy
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Guaiazulene and aureusidin inhibit metabolic adaptability and virulence in Candida albicans by targeting the glyoxylate cycle under alternative carbon conditions
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Discovery of novel azole derivatives with benzanilide-containing hydrophobic side chains for the treatment of drug-resistant fungal infections
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Isavuconazole in the treatment of acute invasive fungal sinusitis: two case reports and literature review
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Self-citation
Vitamin D–AMP axis in host defense against fungal infections
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Targeting Fungal Adaptive Networks and Emerging Molecular Targets for Next-Generation Antifungal Therapeutics
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Increased burden of MDR bacterial infections; reflection from an antibiogram of ICUs of a tertiary care hospital
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Bioactive Heterocyclic Analogs as Antifungal Agents: Recent Advances and Future Aspects
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Zende, A., Pawar, J., Khanwelkar, C. C., Phatak, R., Birla, P. N., & SHIND, M. D. (2025) · Asian Journal of Pharmaceutical and Clinical Research · doi:10.22159/ajpcr.2025v18i6.54631 · Cited by 1 · see citing works
Saccharomyces cerevesiae, Candida spp. and Cryptococcus neoformans β-CAs
Fiore, A. D., Buonanno, M., Esposito, D., D’Ambrosio, K., Langella, E., Simone, G. D., Alterio, V., & Monti, S. M. (2025) · The Enzymes · doi:10.1016/bs.enz.2025.07.001 · Cited by 1 · see citing works
Therapeutic Repurposing of Sertraline: Evidence for Its Antifungal Activity from In Vitro, In Vivo, and Clinical Studies
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In vitro antifungal and antioxidant activity of Cassia singueana stem bark ethanolic extracts and its fractions obtained from Gashua Town, Nigeria
Ali, A. S., Muhammad, A. B., & Lawan, K. A. (2026) · Scientific Reports · doi:10.1038/s41598-026-46897-w · Cited by 1 · see citing works
Design, synthesis and in-silico studies of new triazole–thiazole derivatives as potential antimicrobial agents
Sisode, V., Bhoye, M., Asgaonkar, K. D., Patil, S. M., Pagar, N. S., & Mhaske, P. C. (2026) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2026.146305 · Cited by 1 · see citing works
Design, Synthesis, and Biological Activity Studies of Flavonol Derivatives Containing Isopropanolamine and Piperazine
Qiu, Y., Hu, Q., Hu, C., Li, J., Zhou, Q., Zhang, H., Liu, Z. J., Hao, G., Jin, L., Marambe, B., et al. (2026) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.6c00791 · Cited by 1 · see citing works
Inhibitory effect of Acetylshikonin on drug-resistant Candida albicans
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WHO Critical Priority Fungi: A Comprehensive Review of Antifungal Resistance, Emerging Therapeutic Strategies, and the Potential of Antifungal Peptides
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Hitting them where it hurts: Pantothenate kinase targeting in pathogenic fungi
Pierce, C., & Park, H. (2022) · Structure · doi:10.1016/j.str.2022.10.005
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Enhanced chitosan-based nanoformulation for antifungal applications
Nwachukwu, K. C., Ugbogu, O. C., Oyewole, O. A., Ewansiha, J. U., Adetunji, C. O., Adeyomoye, O., Adetunji, J. B., Ogundolie, F. A., Mathew, J. T., Inobeme, A., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13997-0.00008-4
Biosynthesis of Silver Nanoparticles Using Endophytic Clonostachys rosea ZMS27 from Medicinal Plant Anemarrhena asphodeloides and its Antagonistic Activity Against Superficial Pathogenic Fungi
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Toxicity assessment of methacryloyloxyethyl phosphorylcholine/selenium nanocomposite in case of oral squamous cell carcinoma
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Authors: Cui, X., Wang, L., Lü, Y., & Yue, C.
Affiliations: Yan'an University (CN)
Corresponding author: Lü, Yuhong
Yue, Changwu
ORCID: Lü, Yuhong
Yue, Changwu
Venue: Journal of Infection and Public Health
Publisher: Elsevier BV
Published: 2022-09
Volume: 15
Issue: 9
Pages: 986-1000
ISSN: 1876-0341 (ISSN-L)
DOI: 10.1016/j.jiph.2022.08.004
OpenAlex: W4292083324
Cited by: 85
References: 149
Citations by year: 2026: 18 · 2025: 28 · 2024: 25 · 2023: 13 · 2022: 1
FWCI: 2.58
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Journal of Infection and Public Health (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Natural Science Foundation of China (81860653,82060654)
Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81860653, 82060654)
National College Students Innovation and Entrepreneurship Training Program (S202010719017)
Topics: Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords: antifungal drug development, antifungal resistance, drug-resistant fungi, Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, antifungal drug targets, drug repurposing, immunosuppressants, fungal infection
MeSH terms: Antifungal Agents, Aspergillus fumigatus, Cryptococcus neoformans, Humans, Mycoses

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