{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T12:15:32Z","timestamp":1780920932196,"version":"3.54.1"},"reference-count":111,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100009392","name":"Prince Sattam bin Abdulaziz University","doi-asserted-by":"publisher","award":["PSAU\/2024\/03\/30823"],"award-info":[{"award-number":["PSAU\/2024\/03\/30823"]}],"id":[{"id":"10.13039\/100009392","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Viral diseases, whether pandemic, endemic, or epidemic, are a leading cause of global mortality and disability. Consequently, developing effective viral inhibitors is a critical public health priority. Beyond antiviral drugs, a promising therapeutic strategy involves using immunomodulators, which are antiviral agents that enhance the host's immune system against infection. Phytochemicals (PCHs) derived from plants exhibit diverse bioactive properties, including significant antioxidant and immunomodulatory effects. Notably, PCHs have attracted considerable attention due to their broad\u2010spectrum inhibitory actions against numerous viruses, including SARS\u2010CoV\u20102, dengue virus, hepatitis viruses, and herpes viruses. Recent research has shown how PCHs may target specific signaling pathways implicated in a cytokine storm, a potentially fatal clinical syndrome characterized by an excessive production of pro\u2010inflammatory cytokines and immune cell activation. Numerous studies have investigated the immunomodulatory effects of PCHs on immune function, specifically their ability to regulate key cellular and molecular interactions within the immune system. Additionally, by modulating host immunity, PCHs can enhance the antiviral response. Furthermore, these substances interfere with complex cellular signaling networks, emphasizing their efficacy in preventing viral infections. This review examines the significant and advanced mechanisms PCHs influence immune function during viral illnesses. We subsequently evaluate the potential applications of PCHs as immunomodulatory agents for treating viral infections and discuss their current clinical limitations.<\/jats:p>","DOI":"10.1002\/ptr.70143","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T04:26:38Z","timestamp":1764735998000},"page":"398-419","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Phytochemical\u2010Based Immunomodulation: A Promising Therapeutic Approach for Viral Infections"],"prefix":"10.1002","volume":"40","author":[{"given":"Fahad","family":"Alsaikhan","sequence":"first","affiliation":[{"name":"College of Pharmacy Prince Sattam Bin Abdulaziz University  Alkharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2290-7220","authenticated-orcid":false,"given":"Bagher","family":"Farhood","sequence":"additional","affiliation":[{"name":"Department of Medical Physics and Radiology, Faculty of Paramedical Sciences Kashan University of Medical Sciences  Kashan Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,2]]},"reference":[{"key":"e_1_2_16_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16020218"},{"key":"e_1_2_16_3_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781003340201-16"},{"key":"e_1_2_16_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph17101294"},{"key":"e_1_2_16_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics13100947"},{"key":"e_1_2_16_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116497"},{"issue":"1","key":"e_1_2_16_7_1","article-title":"Immunomodulating Phytochemicals: An Insight Into Their Potential Use in Cytokine Storm Situations","volume":"14","author":"Alarabei A. A.","year":"2023","journal-title":"Advanced Pharmaceutical Bulletin"},{"key":"e_1_2_16_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.637553"},{"key":"e_1_2_16_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.6917"},{"key":"e_1_2_16_10_1","doi-asserted-by":"crossref","unstructured":"Arkhypova \u041c. \u041e.Deriabin \u0422.Trokhymchuk et\u00a0al.2023.\u201cThe Influence of Flavonoid Compositions on Nrf2 Transcription Factor Expression in Case of Infections Triggered by Influenza a Virus and Transmissible Gastroenteritis Coronavirus.\u201d","DOI":"10.20535\/ibb.2023.7.4.290103"},{"key":"e_1_2_16_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202404053"},{"key":"e_1_2_16_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110959"},{"key":"e_1_2_16_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14040381"},{"key":"e_1_2_16_14_1","first-page":"135","article-title":"Unravelling Antileishmanial Mechanisms of Phytochemicals: From Mitochondrial Disruption to Immunomodulation","volume":"4","author":"Bhattacharya S.","year":"2025","journal-title":"Future Integrative Medicine"},{"key":"e_1_2_16_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13337-021-00706-2"},{"key":"e_1_2_16_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2024.148366"},{"issue":"1","key":"e_1_2_16_17_1","first-page":"1","article-title":"Role of Phytochemicals as Immunomodulatory Agents: A Review","volume":"10","author":"Brindha P.","year":"2016","journal-title":"International Journal of Green Pharmacy (IJGP)"},{"key":"e_1_2_16_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11010105"},{"key":"e_1_2_16_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.114316"},{"key":"e_1_2_16_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-99-7261-6_3"},{"key":"e_1_2_16_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14259"},{"key":"e_1_2_16_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155041"},{"key":"e_1_2_16_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwaf190"},{"key":"e_1_2_16_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.970596"},{"key":"e_1_2_16_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1778539"},{"key":"e_1_2_16_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2021.100095"},{"key":"e_1_2_16_27_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X19500678"},{"key":"e_1_2_16_28_1","doi-asserted-by":"publisher","DOI":"10.2174\/0115680266274272240321065039"},{"key":"e_1_2_16_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S295706"},{"key":"e_1_2_16_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15010167"},{"key":"e_1_2_16_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.11.009"},{"key":"e_1_2_16_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22101754"},{"key":"e_1_2_16_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-024-03467-z"},{"key":"e_1_2_16_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amolm.2024.100050"},{"key":"e_1_2_16_35_1","first-page":"1","article-title":"In Silico Study of Antiviral Phytochemicals for the Potential Drug Development Against Wild\u2010Type and Omicron Variants of SARS\u2010CoV\u20102","volume":"26","author":"Dutta S.","year":"2025","journal-title":"Current Pharmaceutical Biotechnology"},{"key":"e_1_2_16_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.742146"},{"key":"e_1_2_16_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/cimb45010003"},{"key":"e_1_2_16_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-15-1761-7_12"},{"key":"e_1_2_16_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1779818"},{"key":"e_1_2_16_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222212385"},{"key":"e_1_2_16_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.8302"},{"issue":"9","key":"e_1_2_16_42_1","first-page":"3396","article-title":"Potential Inhibitors of Coronavirus 3\u2010Chymotrypsin\u2010Like Protease (3CLpro): An In Silico Screening of Alkaloids and Terpenoids From African Medicinal Plants","volume":"39","author":"Gyebi G. A.","year":"2021","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"e_1_2_16_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2011.03.018"},{"key":"e_1_2_16_44_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232213891"},{"key":"e_1_2_16_45_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-023-04303-2"},{"key":"e_1_2_16_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.26829"},{"key":"e_1_2_16_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e23790"},{"key":"e_1_2_16_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/fsn3.70101"},{"key":"e_1_2_16_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006397"},{"key":"e_1_2_16_50_1","first-page":"1","article-title":"Inhibitory Effect of Food\u2010Functioned Phytochemicals on Dysregulated Inflammatory Pathways Triggered by SARS\u2010CoV\u20102: A Mechanistic Review","volume":"65","author":"Jantan I.","year":"2024","journal-title":"Critical Reviews in Food Science and Nutrition"},{"key":"e_1_2_16_51_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S210890"},{"key":"e_1_2_16_52_1","doi-asserted-by":"publisher","DOI":"10.4172\/2168-9652.1000220"},{"key":"e_1_2_16_53_1","first-page":"62","volume-title":"Promising Antiviral Herbal and Medicinal Plants","author":"Kaur S.","year":"2024"},{"key":"e_1_2_16_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1869588"},{"key":"e_1_2_16_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaim.2020.11.004"},{"key":"e_1_2_16_56_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-020-02918-3"},{"key":"e_1_2_16_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29102371"},{"key":"e_1_2_16_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u2010981\u201015\u20100602\u20104_4"},{"key":"e_1_2_16_59_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.606682"},{"key":"e_1_2_16_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.155680"},{"key":"e_1_2_16_61_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1460604"},{"key":"e_1_2_16_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/17435889.2025.2452151"},{"key":"e_1_2_16_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117658"},{"key":"e_1_2_16_64_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6632623"},{"key":"e_1_2_16_65_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9080659"},{"key":"e_1_2_16_66_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-83350-3_8-1"},{"key":"e_1_2_16_67_1","doi-asserted-by":"publisher","DOI":"10.2174\/2211352521666230328123222"},{"key":"e_1_2_16_68_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2023.2194429"},{"issue":"11","key":"e_1_2_16_69_1","first-page":"5328","article-title":"Identification of Phytochemicals From Eclipta Alba and Assess Their Potentiality Against Hepatitis C Virus Envelope Glycoprotein: Virtual Screening, Docking, and Molecular Dynamics Simulation Study","volume":"41","author":"Moharana M.","year":"2023","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"issue":"4","key":"e_1_2_16_70_1","first-page":"3017","article-title":"EGCG Induces \u03b2\u2010Defensin 3 Against Influenza A Virus H1N1 by the MAPK Signaling Pathway","volume":"20","author":"Mou Q.","year":"2020","journal-title":"Experimental and Therapeutic Medicine"},{"key":"e_1_2_16_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjid.2015.10.011"},{"key":"e_1_2_16_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284-025-04064-w"},{"key":"e_1_2_16_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063264"},{"key":"e_1_2_16_74_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1356003"},{"key":"e_1_2_16_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/s44368-024-00004-1"},{"key":"e_1_2_16_76_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1007390"},{"key":"e_1_2_16_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105710"},{"key":"e_1_2_16_78_1","doi-asserted-by":"publisher","DOI":"10.37349\/etat.2025.1002311"},{"key":"e_1_2_16_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16121652"},{"key":"e_1_2_16_80_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox3040649"},{"key":"e_1_2_16_81_1","doi-asserted-by":"publisher","DOI":"10.5493\/wjem.v14.i3.95512"},{"key":"e_1_2_16_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-18776-6.00012-8"},{"key":"e_1_2_16_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.13851"},{"key":"e_1_2_16_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11694-021-01090-7"},{"issue":"3","key":"e_1_2_16_85_1","first-page":"253","article-title":"Bioactive Phytochemicals as Inhibitors Against Dengue Virus Protein NS\u20105 Methyltransferase: In Silico Molecular Docking Approach: Bioactive Phytochemicals as Inhibitors Against Dengue Virus Protein NS\u20105 Methyltransferase","volume":"11","author":"Shakya A. K.","year":"2023","journal-title":"Journal of Ayurveda and Holistic Medicine (JAHM)"},{"key":"e_1_2_16_86_1","doi-asserted-by":"publisher","DOI":"10.2174\/0122113525312781240819105116"},{"key":"e_1_2_16_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.04.174"},{"key":"e_1_2_16_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2022.175332"},{"issue":"9","key":"e_1_2_16_89_1","first-page":"3244","article-title":"An In\u2010Silico Evaluation of Different Saikosaponins for Their Potency Against SARS\u2010CoV\u20102 Using NSP15 and Fusion Spike Glycoprotein as Targets","volume":"39","author":"Sinha S. K.","year":"2021","journal-title":"Journal of Biomolecular Structure and Dynamics"},{"key":"e_1_2_16_90_1","doi-asserted-by":"publisher","DOI":"10.3390\/v17020271"},{"key":"e_1_2_16_91_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297923010066"},{"key":"e_1_2_16_92_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph18052455"},{"key":"e_1_2_16_93_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032657"},{"key":"e_1_2_16_94_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60070-1"},{"key":"e_1_2_16_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e3181719b60"},{"key":"e_1_2_16_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-020-0311-8"},{"key":"e_1_2_16_97_1","doi-asserted-by":"publisher","DOI":"10.1002\/9781394270576.ch6"},{"key":"e_1_2_16_98_1","doi-asserted-by":"publisher","DOI":"10.22146\/ijp.7071"},{"key":"e_1_2_16_99_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2FO02096C"},{"key":"e_1_2_16_100_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.3c00863"},{"key":"e_1_2_16_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e38285"},{"key":"e_1_2_16_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0498-4"},{"key":"e_1_2_16_103_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14122800"},{"key":"e_1_2_16_104_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051344"},{"key":"e_1_2_16_105_1","doi-asserted-by":"publisher","DOI":"10.3390\/ani14203011"},{"key":"e_1_2_16_106_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2015-0528"},{"key":"e_1_2_16_107_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12985-023-02219-4"},{"key":"e_1_2_16_108_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2011.00394.x"},{"key":"e_1_2_16_109_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113555"},{"key":"e_1_2_16_110_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e39176"},{"key":"e_1_2_16_111_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.70011"},{"key":"e_1_2_16_112_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136482"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70143","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70143","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70143","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T12:26:51Z","timestamp":1770380811000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70143"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,2]]},"references-count":111,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/ptr.70143"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70143","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,2]]},"assertion":[{"value":"2025-03-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}