{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:55:30Z","timestamp":1791489330954,"version":"4.3.4"},"reference-count":119,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["82170093"],"award-info":[{"award-number":["82170093"]}]},{"name":"National Natural Science Foundation of China","award":["2023JH2\/20200072"],"award-info":[{"award-number":["2023JH2\/20200072"]}]},{"name":"Liaoning Province Science and Technology Plan Project","award":["82170093"],"award-info":[{"award-number":["82170093"]}]},{"name":"Liaoning Province Science and Technology Plan Project","award":["2023JH2\/20200072"],"award-info":[{"award-number":["2023JH2\/20200072"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Luteolin is a natural flavonoid compound with multifaceted pharmacological properties, including anti-oxidant, anti-inflammatory, antiviral, and anti-tumor activities. Network pharmacology analysis has been utilized to decipher the underlying mechanisms and multitargets of luteolin against coronavirus disease 2019 (COVID-19). This review aims to provide a systematic and comprehensive summary of luteolin, as a potential novel remedy with anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity, as well as its anti-oxidant mechanisms. We systematically delineate the epidemiological profile, genomic architecture, and replicative dynamics of SARS-CoV-2, thereby constructing a multiscale framework to decode its pathogenic mechanisms. Employing a multi-level network pharmacology analytical strategy, we identify 46 core targets through protein interaction network construction, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Molecular investigations reveal luteolin\u2019s dual antiviral mechanisms, including direct targeting of SARS-CoV-2 proteins and host-directed intervention through suppression of angiotensin-converting enzyme 2 receptor engagement\/transmembrane protease serine 2-mediated viral priming. The polypharmacological profile of luteolin demonstrates synergistic effects in blocking viral entry, replication, and host inflammatory cascades. This phytochemical repurposing study of luteolin provides a novel mechanistic paradigm for developing multitarget antiviral agents, highlighting the translational value of natural compounds in combating emerging viral variants.<\/jats:p>","DOI":"10.3390\/ph18091329","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T15:31:21Z","timestamp":1756999881000},"page":"1329","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Anti-Oxidant, Anti-Inflammatory and Antiviral Properties of Luteolin Against SARS-CoV-2: Based on Network Pharmacology"],"prefix":"10.3390","volume":"18","author":[{"given":"Xin","family":"Li","sequence":"first","affiliation":[{"name":"Department of Chemistry, School of Forensic Medicine, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1766-2006","authenticated-orcid":false,"given":"Yunmei","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhe","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9973-6354","authenticated-orcid":false,"given":"Hongguang","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8033-1824","authenticated-orcid":false,"given":"Yan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Stem Cells and Regenerative Medicine, College of Basic Medical Science, China Medical University, Shenyang 110122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41579-020-00459-7","article-title":"Characteristics of SARS-CoV-2 and COVID-19","volume":"19","author":"Hu","year":"2021","journal-title":"Nat. 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