{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T14:52:07Z","timestamp":1775487127143,"version":"3.50.1"},"reference-count":59,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005241","name":"Montreal Clinical Research Institute","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100005241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>H5N1 is a highly pathogenic avian influenza virus of major global concern. Since 2023, it has circulated widely among wild and farmed birds, with increasing spillover into mammals, including minks, seals, and cattle, and sporadic infections in humans in Chile, the UK, and the USA. The risk of a future pandemic is considered high because ongoing viral evolution could enable efficient human-to-human transmission. The hemagglutinin (HA) glycoprotein is the principal determinant of host range, mediating viral attachment and entry through interactions with sialylated glycans and potentially additional host surface proteins. Here, we developed an artificial intelligence (AI)-based pipeline integrating structural modeling, protein\u2013protein interaction prediction, and biological filtering to identify human cell surface proteins with high likelihood of interacting with H5N1 HA. These interactions may contribute to viral entry and tropism and therefore represent promising candidates for experimental validation and therapeutic targeting. Our findings highlight the utility of AI-driven pipelines in accelerating the discovery of host factors relevant to pandemic influenza viruses.<\/jats:p>","DOI":"10.3390\/v17121638","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T15:53:46Z","timestamp":1765986826000},"page":"1638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AI-Powered Identification of Human Cell Surface Protein Interactors of the Hemagglutinin Glycoprotein of High-Pandemic-Risk H5N1 Influenza Virus"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6444-7600","authenticated-orcid":false,"given":"Christian","family":"Poitras","sequence":"first","affiliation":[{"name":"Montreal Clinical Research Institute, 110 Pine Ave West, Montr\u00e9al, QC H2W 1R7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1702-0692","authenticated-orcid":false,"given":"Benoit","family":"Coulombe","sequence":"additional","affiliation":[{"name":"Montreal Clinical Research Institute, 110 Pine Ave West, Montr\u00e9al, QC H2W 1R7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/S0140-6736(97)11212-0","article-title":"Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus","volume":"351","author":"Claas","year":"1998","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1126\/science.279.5349.393","article-title":"Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness","volume":"279","author":"Subbarao","year":"1998","journal-title":"Science"},{"key":"ref_3","unstructured":"WHO (2025, November 09). 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