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While antiviral drugs and vaccines remain the key measures against influenza infection, their limited efficacy and the emergence of resistant viral strains have prompted growing interest in exploring complementary therapeutic approaches. In this review, we critically evaluate current evidence on how plant\u2010derived compounds modulate innate immune signaling networks, including toll\u2010like receptor, retinoic acid\u2010inducible gene I, mitogen\u2010activated protein kinase, and nuclear factor kappa B pathways during IAV infection. We further address the pathway cross\u2010talk that underpins this broad immunomodulatory activity, the translational barriers including bioavailability, metabolic transformation, and standardization that currently limit clinical progression, and the mechanistic gaps that future studies must resolve. Collectively, this review argues that phytocompounds should be understood as modulators of an integrated innate immune network, an insight that reframes both their therapeutic potential and the experimental standards required to advance them.<\/jats:p>","DOI":"10.1002\/mbo3.70424","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:45:59Z","timestamp":1790653559000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Antiviral and Immunomodulatory Effects of Phytochemicals in Influenza A Virus Infection: Targeting Key Host Signaling Pathways"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5633-857X","authenticated-orcid":false,"given":"Dibakar","family":"Chowdhury","sequence":"first","affiliation":[{"name":"Biomedical Sciences &amp; Molecular Biology, College of Medicine and Dentistry James Cook University Townsville Queensland Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University Townsville Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary A.","family":"Vanderven","sequence":"additional","affiliation":[{"name":"Biomedical Sciences &amp; Molecular Biology, College of Medicine and Dentistry James Cook University Townsville Queensland Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University Townsville Queensland Australia"},{"name":"Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity The University of Melbourne Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4381-7382","authenticated-orcid":false,"given":"Phurpa","family":"Wangchuk","sequence":"additional","affiliation":[{"name":"College of Science and Engineering James Cook University Cairns Queensland Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University Cairns Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2685-8377","authenticated-orcid":false,"given":"Subir","family":"Sarker","sequence":"additional","affiliation":[{"name":"Biomedical Sciences &amp; Molecular Biology, College of Medicine and Dentistry James Cook University Townsville Queensland Australia"},{"name":"Australian Institute of Tropical Health and Medicine James Cook University Townsville Queensland Australia"},{"name":"Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment La Trobe University Melbourne Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"issue":"3","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","DOI":"10.1093\/jambio\/lxaf056","article-title":"Plant Extracts as a Source of Antiviral Agents Against Influenza A Virus","volume":"136","author":"Arumugam H.","year":"2025","journal-title":"Journal of Applied Microbiology"},{"key":"e_1_2_15_3_1","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fimmu.2018.00323","article-title":"Induction and Subversion of Human Protective Immunity: Contrasting Influenza and Respiratory Syncytial Virus","volume":"9","author":"Ascough S.","year":"2018","journal-title":"Frontiers in Immunology"},{"issue":"3","key":"e_1_2_15_4_1","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1208\/s12249-010-9520-y","article-title":"Physicochemical Characterization of Berberine Chloride: A Perspective in the Development of a Solution Dosage Form for Oral Delivery","volume":"11","author":"Battu S. 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