{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:15:23Z","timestamp":1790626523379,"version":"4.1.0"},"reference-count":70,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:00:00Z","timestamp":1731542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"1445 AH\/2023 AD","award":["#2023-SDG-I-HMSRC-36570"],"award-info":[{"award-number":["#2023-SDG-I-HMSRC-36570"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Thymoquinone (TQ), a bioactive compound from black cumin (Nigella sativa), has demonstrated a broad range of therapeutic effects. The aim of this study is to evaluate the antifungal efficacy of TQ by targeting key virulence factors in Candida albicans, specifically focusing on isocitrate lyase (ICL) activity, biofilm formation, and gene expression. This study explored TQ\u2019s impact on ICL, a decisive enzyme in the glyoxylate cycle, along with its effect on hyphal formation, biofilm development, and the virulent gene expression of C. albicans through in silico and in vitro studies. Molecular docking revealed a binding energy of \u22126.4 kcal\/mol between TQ and ICL, indicating moderate affinity. The stability of the ICL-TQ complex was validated through 50 ns molecular dynamics simulations, showing the root mean square deviation (RMSD) values of 0.35 nm for ICL and 0.38 nm for the complex. In vitro studies further validated these findings, showing a dose-dependent inhibition of ICL activity. TQ at 2 \u00b5g\/mL reduced enzyme activity by 57%, and at 4 \u00b5g\/mL, by 91.4%. Additionally, TQ disrupted the yeast-to-hyphae switch, a key virulence factor, with 1 and 2 \u00b5g\/mL doses significantly inhibiting hyphal formation. The biofilm formation was similarly affected, with a 58% reduction at 2 \u00b5g\/mL and an 83% reduction at 4 \u00b5g\/mL. TQ also downregulated the ALS1 and HWP1 genes that are associated with adhesion and biofilm development, demonstrating its broad-spectrum antifungal activity. These findings suggest that TQ is a promising candidate for antifungal therapies, targeting multiple virulence factors in C. albicans and potentially overcoming biofilm-associated drug resistance. Future research should focus on in vivo validation, optimization for clinical applications, and expanding its spectrum against other drug-resistant fungal species.<\/jats:p>","DOI":"10.3390\/cimb46110771","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T09:14:31Z","timestamp":1731575671000},"page":"12951-12967","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Silico and In Vitro Studies to Explore the Effect of Thymoquinone on Isocitrate Lyase, Biofilm Formation, and the Expression of Some Virulence Genes in Candida albicans"],"prefix":"10.3390","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-4189","authenticated-orcid":false,"given":"Masood Alam","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraidah 51412, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4623-9557","authenticated-orcid":false,"given":"Mohd","family":"Azam","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraidah 51412, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-1312","authenticated-orcid":false,"given":"Hina","family":"Younus","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1099\/mic.0.030858-0","article-title":"Major roles of isocitrate lyase and malate synthase in bacterial and fungal pathogenesis","volume":"155","author":"Dunn","year":"2009","journal-title":"Microbiology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Lee, Y.V., Wahab, H.A., and Choong, Y.S. 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