{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T19:15:09Z","timestamp":1770837309999,"version":"3.50.1"},"reference-count":90,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Mycetoma is a neglected tropical disease characterised by chronic, granulomatous inflammation of the subcutaneous tissues, often leading to disfigurement, disability, and significant socioeconomic burdens. Caused by a diverse array of bacterial and fungal pathogens, eumycetoma is predominantly driven by\n                    <jats:italic>Madurella mycetomatis<\/jats:italic>\n                    , and current treatment strategies are limited and often ineffective. Conventional antifungal therapies, such as itraconazole, require prolonged administration, frequently combined with surgical interventions, yet cure rates remain suboptimal, and recurrence is common. The formidable protective grain, comprising microbial material, melanin, and host-derived substances, acts as a physical and biochemical barrier, impeding the penetration and efficacy of drugs. Additionally, issues such as toxicity, resistance, and high costs further complicate management, underscoring the urgent need for novel therapeutic strategies. Recent advancements in computational drug discovery, particularly molecular docking, offer promising avenues to accelerate the identification of effective anti-mycetoma agents. Molecular docking simulates the interaction between small molecules and target proteins, enabling rapid virtual screening of large compound libraries, including natural products, existing drugs, and synthetic molecules, against key pathogenic targets. This structure-based approach helps prioritise candidates with high binding affinity, guiding subsequent experimental validation and reducing both time and financial costs associated with traditional drug development. When integrated with artificial intelligence (AI) and machine learning (ML), these methods can enhance predictive accuracy, uncover novel bioactive scaffolds, and facilitate the repurposing of FDA-approved drugs such as montelukast and vilanterol. Key molecular targets in\n                    <jats:italic>M. mycetomatis<\/jats:italic>\n                    include enzymes and pathways critical for pathogen survival and virulence, notably cytochrome P450 (CYP51), dihydrofolate reductase (DHFR), chitin synthase, melanin biosynthesis pathways, and metal ion acquisition systems. Melanin production, via DHN-melanin, DOPA-melanin, and pyomelanin pathways, contributes to grain pigmentation and structural integrity, while metal ions such as iron and zinc are vital for enzymatic activities, grain formation, and fungal virulence. Disrupting metal ion homeostasis through targeting zincophores, siderophores, and zinc-binding proteins represents a promising therapeutic strategy to weaken grain robustness and enhance drug penetration. Despite the potential of molecular docking, limitations such as reliance on homology models, static protein structures, and the absence of cellular context necessitate complementary approaches, including molecular dynamics simulations and in vitro validation. These combined efforts can refine candidate compounds, optimise binding affinities, and predict pharmacokinetic properties. Furthermore, integrating docking results with clinical data and global collaboration platforms can accelerate the discovery of affordable, effective treatments tailored to endemic regions. In conclusion, leveraging molecular docking and computational methods to target essential\n                    <jats:italic>M. mycetomatis<\/jats:italic>\n                    pathways offers a promising frontier in mycetoma research. By identifying novel inhibitors and understanding pathogen biology at a molecular level, these approaches can inform targeted therapies, reduce treatment durations, and improve patient outcomes. Future research should focus on validating computational predictions experimentally and translating these findings into clinical practice, with an emphasis on accessible, cost-effective interventions for vulnerable populations affected by this neglected disease.\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0013963","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:27:43Z","timestamp":1770834463000},"page":"e0013963","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular docking approaches in mycetoma: Toward improved patient management"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3524-4825","authenticated-orcid":true,"given":"Ali Awadallah","family":"Saeed","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marwa Salah S.","family":"Osman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmed Hassan","family":"Fahal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"pntd.0013963.ref001","article-title":"Eumycetoma","volume-title":"StatPearls","author":"S Yadlapati","year":"2025"},{"issue":"3","key":"pntd.0013963.ref002","doi-asserted-by":"crossref","first-page":"97","DOI":"10.3390\/tropicalmed3030097","article-title":"Mycetoma: the spectrum of clinical presentation","volume":"3","author":"AH Fahal","year":"2018","journal-title":"Trop Med Infect Dis"},{"issue":"1","key":"pntd.0013963.ref003","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1590\/abd1806-4841.20187075","article-title":"Mycetomas: an epidemiological, etiological, clinical, laboratory and therapeutic review","volume":"93","author":"CMS 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Gutierrez-Gongora","year":"2021","journal-title":"J Fungi (Basel)"},{"issue":"12","key":"pntd.0013963.ref077","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.4155\/fmc-2016-0110","article-title":"The GPI anchor pathway: a promising antifungal target?","volume":"8","author":"M Mutz","year":"2016","journal-title":"Future Med Chem"},{"issue":"12","key":"pntd.0013963.ref078","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.3390\/microorganisms10122469","article-title":"Fungal Zinc homeostasis and its potential as an antifungal target: a focus on the human pathogen Aspergillus fumigatus","volume":"10","author":"P Zhai","year":"2022","journal-title":"Microorganisms"},{"issue":"1","key":"pntd.0013963.ref079","doi-asserted-by":"crossref","first-page":"315","DOI":"10.3390\/ijms26010315","article-title":"Repurposing FDA-approved drugs for eumycetoma treatment: homology modeling and computational screening of CYP51 inhibitors","volume":"26","author":"MA Mohamed","year":"2025","journal-title":"Int J Mol Sci"},{"issue":"1","key":"pntd.0013963.ref080","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12896-025-00948-8","article-title":"Antifungal activity and biocompatibility assessment with molecular docking and dynamic simulations of new pyrazole derivatives","volume":"25","author":"BT Abd-Elhalim","year":"2025","journal-title":"BMC Biotechnol"},{"issue":"11","key":"pntd.0013963.ref081","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1002\/prot.26164","article-title":"Repurposing of FDA-approved drugs against active site and potential allosteric drug-binding sites of COVID-19 main protease","volume":"89","author":"M Yuce","year":"2021","journal-title":"Proteins"},{"key":"pntd.0013963.ref082","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/978-1-4939-9752-7_2","article-title":"Integrating molecular docking and molecular dynamics simulations","volume":"2053","author":"LHS Santos","year":"2019","journal-title":"Methods Mol Biol"},{"key":"pntd.0013963.ref083","unstructured":"Awad TA, Abd Algaffar SO, van de Sande WW, Khalid SA. Molecular docking based on homology modelling of 4-\u03b1-lanosterol demethylase (CYP51) from Madurella mycetomatis. 2018."},{"issue":"11","key":"pntd.0013963.ref084","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1038\/s41594-023-01097-2","article-title":"Structure reveals why genome folding is necessary for site-specific integration of foreign DNA into CRISPR arrays","volume":"30","author":"A Santiago-Frangos","year":"2023","journal-title":"Nat Struct Mol Biol"},{"issue":"4","key":"pntd.0013963.ref085","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3390\/applbiosci4040048","article-title":"Impact of structural relaxation on protein\u2013protein docking in large macromolecular complexes","volume":"4","author":"L Rosa RS de","year":"2025","journal-title":"Appl Biosci"},{"issue":"1","key":"pntd.0013963.ref086","doi-asserted-by":"crossref","first-page":"13398","DOI":"10.1038\/s41598-023-40160-2","article-title":"Molecular docking as a tool for the discovery of molecular targets of nutraceuticals in diseases management","volume":"13","author":"PC Agu","year":"2023","journal-title":"Sci Rep"},{"issue":"2","key":"pntd.0013963.ref087","doi-asserted-by":"crossref","first-page":"146","DOI":"10.2174\/157340911795677602","article-title":"Molecular docking: a powerful approach for structure-based drug discovery","volume":"7","author":"X-Y Meng","year":"2011","journal-title":"Curr Comput Aided Drug Des"},{"issue":"18","key":"pntd.0013963.ref088","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.3390\/ijms20184331","article-title":"Molecular docking: shifting paradigms in drug discovery","volume":"20","author":"L Pinzi","year":"2019","journal-title":"Int J Mol Sci"},{"issue":"4","key":"pntd.0013963.ref089","article-title":"Addressing the most neglected diseases through an open research model: the discovery of fenarimols as novel drug candidates for eumycetoma","volume":"12","author":"W Lim","year":"2018","journal-title":"PLoS Negl Trop Dis"},{"issue":"8","key":"pntd.0013963.ref090","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.3390\/ijms11083016","article-title":"Advances and challenges in protein-ligand docking","volume":"11","author":"S-Y Huang","year":"2010","journal-title":"Int J Mol Sci"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013963","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:27:53Z","timestamp":1770834473000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0013963"}},"subtitle":[],"editor":[{"given":"Francelise","family":"Bridi Cavassin","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,2,11]]},"references-count":90,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2,11]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0013963","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,11]]}}}