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Despite the known antiviral and anticancer properties of\n                      <jats:italic>Ganoderma lucidum<\/jats:italic>\n                      , its specific molecular mechanisms against EBV\u2010mediated DLBCL remain unexplored. Therefore, this study aimed to investigate the potential multi\u2010target inhibitory mechanisms of\n                      <jats:italic>G. lucidum<\/jats:italic>\n                      compounds against EBV\u2010associated DLBCL by integrating absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling of 1046 compounds; network pharmacology analysis for target identification; transcriptomic evaluation using DLBCL patient datasets from The Cancer Genome Atlas (TCGA) and Genotype\u2010Tissue Expression (GTEx) (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a047 tumors,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0337 normals); molecular docking; density functional theory (DFT) calculations; machine learning\u2013based activity prediction, molecular dynamics (MD) simulations; and Molecular Mechanics Poisson\u2013Boltzmann Surface Area (MM\u2013PBSA) binding free energy calculations. Eight compounds (kobusin, chrysin, dalbergin, galangin, isorhamnetin, lauric acid, piperbetol, and vitamin D3) demonstrated favorable ADMET profiles. Network pharmacology analysis identified 217 common targets, with AKT1 and BCL2 significantly upregulated in DLBCL tumors. Isorhamnetin showed the strongest AKT1 binding (\u22128.33\u00a0kcal\/mol), surpassing control (\u22125.11\u00a0kcal\/mol), whereas galangin exhibited the highest BCL2 affinity (\u22126.13\u00a0kcal\/mol), outperforming control (\u22125.23\u00a0kcal\/mol). Random forest achieved cross\u2010validation scores of 0.8634\u00a0\u00b1\u00a00.0158 for AKT1 and 0.8965\u00a0\u00b1\u00a00.0146 for BCL2, predicting IC\n                      <jats:sub>50<\/jats:sub>\n                      &lt;1000\u00a0nM for all compounds. MD simulations confirmed the binding stability of all compounds with low root mean square deviation (RMSD, &lt;2.5\u00a0\u00c5). MM\u2013PBSA calculations revealed favorable binding free energies of \u221223.01\u00a0kcal\/mol (AKT1\u2010galangin), \u221219.01\u00a0kcal\/mol (AKT1\u2010isorhamnetin), \u221232.15\u00a0kcal\/mol (BCL2\u2010isorhamnetin), and \u221228.97\u00a0kcal\/mol (BCL2\u2010galangin). Therefore, isorhamnetin and galangin may have multi\u2010target inhibitory potential against AKT1 and BCL2, providing a robust foundation for further in vitro and in vivo validation as therapeutic candidates for EBV\u2010mediated DLBCL intervention.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Practical Applications<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Ganoderma lucidum<\/jats:italic>\n                      is a medicinal mushroom widely used in traditional and functional food applications and may serve as a source of natural anticancer compounds with potential benefits for EBV\u2010associated diffuse large B\u2010cell lymphoma. The multi\u2010targeting potential of\n                      <jats:italic>G. lucidum<\/jats:italic>\n                      \u2013derived bioactive constituents, isorhamnetin and galangin, against AKT1 and BCL2 may position it as a promising functional food\u2010based candidate for anticancer therapeutics.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.71575","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:41:20Z","timestamp":1792395680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring Potential Multi\u2010Target Inhibition Mechanisms of\n                    <i>Ganoderma lucidum<\/i>\n                    Against EBV\u2010Mediated DLBCL Using Integrative Bioinformatics, Machine Learning, and Network Pharmacology Approaches"],"prefix":"10.1111","volume":"91","author":[{"given":"Azrin","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Mawlana Bhashani Science and Technology University  Tangail Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Abdul","family":"Kader","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Mawlana Bhashani Science and Technology University  Tangail Bangladesh"},{"name":"Department of Bioscience and Biotechnology Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3923-1266","authenticated-orcid":false,"given":"Sheikh Abdullah","family":"Al Ashik","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Genetic Engineering Mawlana Bhashani Science and Technology University  Tangail 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