{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T09:52:06Z","timestamp":1791539526022,"version":"4.3.4"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,24]],"date-time":"2025-08-24T00:00:00Z","timestamp":1755993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Beijing Nova Program","award":["20240484733"],"award-info":[{"award-number":["20240484733"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza A virus pandemics pose a persistent global health threat, and emerging antiviral resistance underscores the critical importance of developing novel broad-spectrum therapeutic agents. Building on licorice\u2019s (Glycyrrhiza spp.) historical use in traditional Chinese medicine for respiratory infections\u2014as documented in the Chinese Guidelines for Diagnosis and Treatment of Influenza\u2014and its demonstrated anti-SARS-CoV-2 activity, we identified licoflavone B as a potent anti-influenza agent, bridging ethnopharmacological knowledge with mechanistic validation. In this study, we identified licoflavone B, a natural flavonoid derived from licorice (Glycyrrhiza spp.), as a potent inhibitor of diverse influenza viruses, including multiple influenza A subtypes and type B virus. Mechanistic studies revealed that licoflavone B selectively targets the viral RNA-dependent RNA polymerase (RdRp), effectively suppressing viral replication. The compound exhibits a favorable selectivity index (SI = 14.9\u201329.9), indicating a promising therapeutic window. Molecular docking simulations identified potential binding interactions between licoflavone B and regions of the RdRp complex, which were further validated by dose-dependent inhibition of viral nucleoprotein (NP) and polymerase subunit PB2 expression in Western blot and immunofluorescence assays. In addition, licoflavone B maintained broad-spectrum antiviral activity against multiple influenza strains, including H1N1 (A\/Puerto Rico\/8\/34), H3N2 (A\/Darwin\/9\/2021), and a clinical influenza B isolate (B\/Beijing\/ZYY-B18\/2018). These findings position licoflavone B as a promising lead compound for developing next-generation, broad-spectrum antiviral therapies against influenza and potentially other viruses.<\/jats:p>","DOI":"10.3390\/v17091157","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:09:32Z","timestamp":1756080572000},"page":"1157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Licoflavone B Suppresses Influenza A Virus by Targeting the Viral RNA-Dependent RNA Polymerase (RdRp)"],"prefix":"10.3390","volume":"17","author":[{"given":"Pu","family":"Fan","sequence":"first","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5719-7997","authenticated-orcid":false,"given":"Peng","family":"Lv","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1090-3193","authenticated-orcid":false,"given":"Sen","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewen","family":"Qian","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Cui","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Feng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeya","family":"Li","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Qiang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzhu","family":"Dong","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Fang","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1908-2926","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changming","family":"Yu","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0580-5997","authenticated-orcid":false,"given":"Xiangyang","family":"Chi","sequence":"additional","affiliation":[{"name":"Academy of Military Medical Sciences, Beijing 100071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.2217\/fmb.13.81","article-title":"Avian influenza: Virology, diagnosis and surveillance","volume":"8","author":"Bustin","year":"2013","journal-title":"Future Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/nrmicro2613","article-title":"Influenza A viruses: New research developments","volume":"9","author":"Medina","year":"2011","journal-title":"Nat. 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