{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:19:09Z","timestamp":1788153549320,"version":"build-2803163510"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:00:00Z","timestamp":1787961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Lingang Laboratory","award":["LGL-2615-02"],"award-info":[{"award-number":["LGL-2615-02"]}]},{"name":"Lingang Laboratory","award":["LGL-2615-07"],"award-info":[{"award-number":["LGL-2615-07"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2023-I2M-2-006"],"award-info":[{"award-number":["2023-I2M-2-006"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2025-I2M-KJ-019"],"award-info":[{"award-number":["2025-I2M-KJ-019"]}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2024-I2M-TS-016"],"award-info":[{"award-number":["2024-I2M-TS-016"]}]},{"name":"National Foreign Expert Project of Ministry of Human Resources and Social Security of the People\u2019s Republic of China","award":["S20240248"],"award-info":[{"award-number":["S20240248"]}]},{"award":["S20240248"],"award-info":[{"award-number":["S20240248"]}],"id":[{"id":"https:\/\/ror.org\/01kjwqy11","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81370087"],"award-info":[{"award-number":["81370087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"award":["81370087"],"award-info":[{"award-number":["81370087"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Rising drug resistance undermines current anti-influenza virus therapies. Although targeting the hemagglutinin (HA)\u2013sialic acid receptor interaction is a promising strategy, progress is impeded by the lack of subtype-independent screening models. Herein, we established a fluorescence-based cell high-throughput model using fluorescein isothiocyanate-conjugated Sambucus Nigra Lectin (FITC-SNA) as a stable HA surrogate and \u03b1-2,6-sialyltransferase (ST6GAL1)-overexpressing MDCK cells to mimic the HA\u2013receptor interface. This platform was designed to serve as an efficient primary screening tool to rapidly filter large compound libraries for potential binders to the receptor-binding interface. Screening 10,000 compounds identified Obatoclax Mesylate and Ethylparaben as primary hits. Both exhibited broad-spectrum HA inhibition activity, validating the model\u2019s capability to identify compounds interfering with viral attachment. Further cellular antiviral assays revealed cytotoxicity for both compounds, resulting in low selectivity indexes (SIs), indicating that while these molecules effectively target the interaction site, they require substantial structural optimization for therapeutic use. Molecular docking confirmed their binding to type A H1N1, H3N2, and B\/Victoria HA proteins, while ADMET predictions highlighted specific structural optimization needs to mitigate toxicity. In conclusion, this subtype-independent, highly specific high-throughput screening (HTS) model provides an efficient and reliable platform for early-stage influenza drug discovery and lead compound development.<\/jats:p>","DOI":"10.3390\/biom16091253","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:08:58Z","timestamp":1788142138000},"page":"1253","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Cell-Based High-Throughput Screening Model for Inhibitors Targeting Influenza Virus Hemagglutinin\u2013\u03b1-2,6-Sialic Acid Interaction"],"prefix":"10.3390","volume":"16","author":[{"given":"Keyu","family":"Guo","sequence":"first","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Xiaofang","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Chenyin","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Yaru","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Chao","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"}]},{"given":"Yexiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Xiuyong","family":"Fan","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Yanni","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Shuyi","family":"Si","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0950-9455","authenticated-orcid":false,"given":"Yongxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, 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Drug Discov."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1253\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:30:10Z","timestamp":1788150610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1253"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,29]]},"references-count":41,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091253"],"URL":"https:\/\/doi.org\/10.3390\/biom16091253","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,29]]}}}