{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:14:03Z","timestamp":1785428043639,"version":"3.56.0"},"reference-count":58,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T00:00:00Z","timestamp":1781481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"China National Natural Science Foundation","doi-asserted-by":"crossref","award":["82341098"],"award-info":[{"award-number":["82341098"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["82341098"],"award-info":[{"award-number":["82341098"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The influenza A virus (IAV) has been responsible for multiple seasonal epidemics and poses a pandemic threat, and the growing number of variant strains constitutes a persistent threat to humanity. This study aimed to identify anti-influenza compounds from a traditional Chinese medicine (TCM) monomer library using a machine learning approach, with calmodulin as a hypothesis-driven target. The antiviral efficacy of the compounds with the highest predicted binding scores from virtual screening was evaluated using integrated computational and experimental approaches. A pre-trained protein language model (ConPLex) was employed for virtual screening. Molecular docking was used to predict binding characteristics, and network pharmacology was applied to generate hypotheses on multi-target mechanisms. The cytotoxicity and anti-H1N1 activity of the selected compounds were assessed in vitro, followed by in vivo evaluation of survival, lung pathology, viral load, and inflammatory mediators in a lethal mouse infection model. Sodium deoxycholate (NaDC) and deoxycholic acid (DCA) were identified as promising lead compounds. Both exhibited dose-dependent inhibition of viral replication in vitro with low cytotoxicity. Treatment with NaDC and DCA significantly improved survival rates and reduced lung pathology in H1N1-infected mice. Treatment was associated with suppression of nuclear factor kappa-B (NF-\u03baB) activation, reduced pro-inflammatory cytokines, and elevated interleukin-10 (IL-10) levels. Molecular docking predictions indicated that NaDC and DCA exhibit moderate binding affinity for calmodulin, with binding energies of \u22128.38 kcal\/mol and \u22127.61 kcal\/mol, respectively. Furthermore, network pharmacology analysis suggested that these compounds may modulate pathways related to viral infection, inflammation, and immune regulation. NaDC and DCA demonstrate anti-influenza activity both in vitro and in vivo, reducing viral replication and alleviating inflammatory lung injury. These findings position NaDC and DCA as promising lead compounds for anti-influenza drug development and provide a foundation for further mechanistic validation.<\/jats:p>","DOI":"10.3390\/ijms27125399","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:49:01Z","timestamp":1781570941000},"page":"5399","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Machine Learning and Experimental Verification Identify Anti-Influenza Natural Products"],"prefix":"10.3390","volume":"27","author":[{"given":"Feifan","family":"Qiu","sequence":"first","affiliation":[{"name":"College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajing","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Cao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuena","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Xue","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5152-7722","authenticated-orcid":false,"given":"Yueqi","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Bu","sequence":"additional","affiliation":[{"name":"College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beilei","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Gao","sequence":"additional","affiliation":[{"name":"College of Integrated Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun 130117, China"},{"name":"State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun 130122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nogrady, B. 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