{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T15:46:39Z","timestamp":1785685599796,"version":"3.56.0"},"reference-count":111,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,26]],"date-time":"2023-01-26T00:00:00Z","timestamp":1674691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100940"],"award-info":[{"award-number":["32100940"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["buctrc202230"],"award-info":[{"award-number":["buctrc202230"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundamental Research Funds for the Central Universities","award":["32100940"],"award-info":[{"award-number":["32100940"]}]},{"name":"Fundamental Research Funds for the Central Universities","award":["buctrc202230"],"award-info":[{"award-number":["buctrc202230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Influenza virus has continuously spread around the globe for more than 100 years since the first influenza epidemic in 1918. The rapid and unpredictable gene variation of the influenza virus could possibly bring about another pandemic in future, which might threaten to overwhelm us without adequate preparation. Consequently, it is extremely urgent to identify effective broad-spectrum antiviral treatments for a variety of influenza virus variants. As essential body components, trace elements are great potential candidates with an as yet poorly understood ability to protect the host from influenza infection. Herein, we have summarized the present state of knowledge concerning the function of trace elements in influenza virus replication along with an analysis of their potential molecular mechanisms. Modulation of host immune responses to the influenza virus is one of the most common modes to achieve the anti-influenza activity of trace elements, such as selenium and zinc. Simultaneously, some antioxidant and antiviral signal pathways can be altered with the participation of trace elements. More interestingly, some micro-elements including selenium, zinc, copper and manganese, directly target viral proteins and regulate their stability and activity to influence the life cycle of the influenza virus. Further verification of the antiviral effect and the mechanism will promote the application of trace elements as adjuvants in the clinic.<\/jats:p>","DOI":"10.3390\/metabo13020184","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T01:27:58Z","timestamp":1674782878000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Non-Negligible Role of Trace Elements in Influenza Virus Infection"],"prefix":"10.3390","volume":"13","author":[{"given":"Shan","family":"Xu","sequence":"first","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanyang","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenqi","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinglin","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8503-8045","authenticated-orcid":false,"given":"Yigang","family":"Tong","sequence":"additional","affiliation":[{"name":"College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100089, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,26]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023, January 10). Up to 650 000 People Die of Respiratory Diseases Linked to Seasonal Flu Each Year. Available online: https:\/\/www.who.int\/news\/item\/13-12-2017-up-to-650-000-people-die-of-respiratory-diseases-linked-to-seasonal-flu-each-year."},{"key":"ref_2","unstructured":"CDC (2023, January 10). Types of Influenza Viruses, Available online: https:\/\/www.cdc.gov\/flu\/about\/viruses\/types.htm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1017\/S1431927620000069","article-title":"Filamentous Versus Spherical Morphology: A Case Study of the Recombinant a\/Wsn\/33 (H1n1) Virus","volume":"26","author":"Kordyukova","year":"2020","journal-title":"Microsc. Microanal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-018-0002-y","article-title":"Influenza","volume":"4","author":"Krammer","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_5","unstructured":"FDA (2023, January 10). Influenza (Flu) Antiviral Drugs and Related Information, Available online: https:\/\/www.fda.gov\/drugs\/information-drug-class\/influenza-flu-antiviral-drugs-and-related-information."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1186\/s12985-019-1258-x","article-title":"Influenza a Virus Hemagglutinin Mutations Associated with Use of Neuraminidase Inhibitors Correlate with Decreased Inhibition by Anti-Influenza Antibodies","volume":"16","author":"Ilyushina","year":"2019","journal-title":"Virol. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e01639-18","DOI":"10.1128\/JVI.01639-18","article-title":"Mutations in Influenza a Virus Neuraminidase and Hemagglutinin Confer Resistance against a Broadly Neutralizing Hemagglutinin Stem Antibody","volume":"93","author":"Prachanronarong","year":"2019","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"12878","DOI":"10.1073\/pnas.1717159115","article-title":"Why the Evolution of Vaccine Resistance Is Less of a Concern Than the Evolution of Drug Resistance","volume":"115","author":"Kennedy","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Nieder, R., Benbi, D.K., and Reichl, F.X. (2018). Microelements and Their Role in Human Health, Springer.","DOI":"10.1007\/978-94-024-1222-2_7"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Islam, M.R., Akash, S., Jony, M.H., Alam, M.N., Nowrin, F.T., Rahman, M.M., Rauf, A., and Thiruvengadam, M. (2023). Exploring the potential function of trace elements in human health: A therapeutic perspective. Mol. Cell Biochem., 1\u201331.","DOI":"10.1007\/s11010-022-04638-3"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1007\/s12011-021-02733-y","article-title":"Are Essential Trace Elements Effective in Modulation of Mental Disorders? Update and Perspectives","volume":"200","author":"Shayganfard","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Dubey, P., Thakur, V., and Chattopadhyay, M. (2020). Role of Minerals and Trace Elements in Diabetes and Insulin Resistance. Nutrients, 12.","DOI":"10.3390\/nu12061864"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1136\/jim-2018-000833","article-title":"Association between trace element concentrations and anemia in patients with chronic kidney disease: A cross-sectional population-based study","volume":"67","author":"Pan","year":"2019","journal-title":"J. Investig. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/1055-9965.EPI-18-0286","article-title":"Exposure to Trace Elements and Risk of Skin Cancer: A Systematic Review of Epidemiologic Studies","volume":"28","author":"Matthews","year":"2019","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Shimada, B.K., Alfulaij, N., and Seale, L.A. (2021). The Impact of Selenium Deficiency on Cardiovascular Function. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221910713"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Luster, M., Duntas, L., and Wartofsky, L. (2019). The Thyroid and Its Diseases. Selenium Deficiency and Thyroid Disease, Springer.","DOI":"10.1007\/978-3-319-72102-6"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Lammi, M.J., and Qu, C. (2018). Selenium-Related Transcriptional Regulation of Gene Expression. Int. J. Mol. Sci., 19.","DOI":"10.20944\/preprints201808.0087.v1"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1038\/aps.2018.25","article-title":"Zinc deficiency and cellular oxidative stress: Prognostic implications in cardiovascular diseases","volume":"39","author":"Choi","year":"2018","journal-title":"Acta Pharm. Sin."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"717064","DOI":"10.3389\/fnut.2022.717064","article-title":"Mechanistic Impact of Zinc Deficiency in Human Development","volume":"9","author":"Hussain","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.3389\/fmed.2022.1093868","article-title":"Trace Element Zinc and Skin Disorders","volume":"9","author":"Zou","year":"2023","journal-title":"Front. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(20)32594-0","article-title":"Iron Deficiency","volume":"397","author":"Pasricha","year":"2021","journal-title":"Lancet"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1093\/eurheartj\/ehac569","article-title":"Iron Deficiency and Cardiovascular Disease","volume":"44","author":"Savarese","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.fct.2015.10.006","article-title":"Toxic Trace Elements at Gastrointestinal Level","volume":"86","author":"Vazquez","year":"2015","journal-title":"Food Chem. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1007\/s10534-022-00444-y","article-title":"Multielement Determination (Essential and Potentially Toxic Elements) in Eye Shadows Exposed to Consumption in Brazil Using Icp Oes","volume":"35","author":"Santana","year":"2022","journal-title":"Biometals"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Pecora, F., Persico, F., Argentiero, A., Neglia, C., and Esposito, S. (2020). The Role of Micronutrients in Support of the Immune Response against Viral Infections. Nutrients, 12.","DOI":"10.3390\/nu12103198"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2556","DOI":"10.1007\/s12011-021-02859-z","article-title":"Zinc and Respiratory Viral Infections: Important Trace Element in Anti-Viral Response and Immune Regulation","volume":"200","author":"Sadeghsoltani","year":"2022","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1017\/S0007114522000083","article-title":"Vitamins, Microelements and the Immune System: Current Standpoint in the Fight against Coronavirus Disease 2019","volume":"128","author":"Djordjevic","year":"2022","journal-title":"Br. J. Nutr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1016\/j.freeradbiomed.2007.03.017","article-title":"Selenium Deficiency Alters Epithelial Cell Morphology and Responses to Influenza","volume":"42","author":"Jaspers","year":"2007","journal-title":"Free Radic Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1039\/D1RA08658H","article-title":"Selenium Nanoparticles Inhibited H1n1 Influenza Virus-Induced Apoptosis by Ros-Mediated Signaling Pathways","volume":"12","author":"Liu","year":"2022","journal-title":"RSC Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.vetimm.2018.12.002","article-title":"Dietary Selenium Supplementation Enhances Antiviral Immunity in Chickens Challenged with Low Pathogenic Avian Influenza Virus Subtype H9n2","volume":"207","author":"Shojadoost","year":"2019","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1007\/s12011-010-8726-x","article-title":"Protection from H1n1 Influenza Virus Infections in Mice by Supplementation with Selenium: A Comparison with Selenium-Deficient Mice","volume":"141","author":"Yu","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1096\/fj.00-0721fje","article-title":"Selenium Deficiency Increases the Pathology of an Influenza Virus Infection","volume":"15","author":"Beck","year":"2001","journal-title":"FASEB J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s40104-022-00706-2","article-title":"The Health Benefits of Selenium in Food Animals: A Review","volume":"13","author":"Pecoraro","year":"2022","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtemb.2007.10.002","article-title":"Effects of Selenium Status and Supplementary Seleno-Chemical Sources on Mouse T-Cell Mitogenesis","volume":"22","author":"Ueno","year":"2008","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1007\/s00705-016-3187-y","article-title":"Implications of Oxidative Stress on Viral Pathogenesis","volume":"162","author":"Camini","year":"2017","journal-title":"Arch. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8002","DOI":"10.1039\/C9RA09524A","article-title":"The Inhibition of H1n1 Influenza Induced Apoptosis by Sodium Selenite through Ros-Mediated Signaling Pathways","volume":"10","author":"Gong","year":"2020","journal-title":"RSC Adv."},{"key":"ref_37","first-page":"8002","article-title":"Selenoproteins Mediate T Cell Immunity through an Antioxidant Mechanism","volume":"10","author":"Shrimali","year":"2008","journal-title":"RSC Adv."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.4049\/jimmunol.143.4.1210","article-title":"Il-2 and Ifn-Gamma Are Two Necessary Lymphokines in the Development of Cytolytic T Cells","volume":"143","author":"Maraskovsky","year":"1989","journal-title":"J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/383787a0","article-title":"Functional Diversity of Helper T Lymphocytes","volume":"383","author":"Abbas","year":"1996","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s002440010101","article-title":"Increased Production of Proinflammatory Cytokines by Murine Macrophages Following Oral Exposure to Sodium Selenite but Not to Seleno-L-Methionine","volume":"39","author":"Johnson","year":"2000","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s12011-011-8977-1","article-title":"Review: Micronutrient Selenium Deficiency Influences Evolution of Some Viral Infectious Diseases","volume":"143","author":"Harthill","year":"2011","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"34504","DOI":"10.1074\/jbc.M111.262048","article-title":"Biochemical Impact of the Host Adaptation-Associated Pb2 E627k Mutation on the Temperature-Dependent Rna Synthesis Kinetics of Influenza a Virus Polymerase Complex","volume":"286","author":"Aggarwal","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6855","DOI":"10.1074\/jbc.C800224200","article-title":"Structural Basis of the Influenza a Virus Rna Polymerase Pb2 Rna-Binding Domain Containing the Pathogenicity-Determinant Lysine 627 Residue","volume":"284","author":"Kuzuhara","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1099\/vir.0.83419-0","article-title":"H5n1 Avian Influenza Re-Emergence of Lake Qinghai: Phylogenetic and Antigenic Analyses of the Newly Isolated Viruses and Roles of Migratory Birds in Virus Circulation","volume":"89","author":"Wang","year":"2008","journal-title":"J. Gen. Virol."},{"key":"ref_45","first-page":"105","article-title":"Selenium Contents in the Blood of Grazing Yaks and Rangeland Plants in the Eastern Tibet-High Plateau, China","volume":"39","author":"Song","year":"2003","journal-title":"Jpn. J. Livest. Manag."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"772","DOI":"10.3201\/eid1305.061209","article-title":"Avian Influenza (H5n1) Virus in Waterfowl and Chickens, Central China","volume":"13","author":"Yu","year":"2007","journal-title":"Emerg. Infect Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1016\/S0883-2927(01)00046-4","article-title":"Biogeochemical Cycling of Selenium in Chinese Environments","volume":"16","author":"Wang","year":"2001","journal-title":"Appl. Geochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1096\/fj.01-0108com","article-title":"Host Nutritional Selenium Status as a Driving Force for Influenza Virus Mutations","volume":"15","author":"Nelson","year":"2001","journal-title":"FASEB J."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.tim.2004.07.007","article-title":"Host Nutritional Status: The Neglected Virulence Factor","volume":"12","author":"Beck","year":"2004","journal-title":"Trends Microbiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/advances\/nmz013","article-title":"The Role of Zinc in Antiviral Immunity","volume":"10","author":"Read","year":"2019","journal-title":"Adv. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"970","DOI":"10.2105\/AJPH.2009.187773","article-title":"Zinc Intake and Resistance to H1n1 Influenza","volume":"100","author":"Sandstead","year":"2010","journal-title":"Am. J. Public Health"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e003176","DOI":"10.1136\/bmjgh-2020-003176","article-title":"Effect of Micronutrient Supplements on Influenza and Other Respiratory Tract Infections among Adults: A Systematic Review and Meta-Analysis","volume":"6","author":"Abioye","year":"2021","journal-title":"BMJ Glob. Health."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12929-019-0563-4","article-title":"Inhibition of H1n1 Influenza Virus Infection by Zinc Oxide Nanoparticles: Another Emerging Application of Nanomedicine","volume":"26","author":"Ghaffari","year":"2019","journal-title":"J. Biomed. Sci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1177\/095632020701800302","article-title":"Effect of Oral Gavage Treatment with Znal42 and Other Metallo-Ion Formulations on Influenza a H5n1 and H1n1 Virus Infections in Mice","volume":"18","author":"Barnard","year":"2007","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s12985-021-01585-1","article-title":"Combination Therapy of Zinc and Trimethoprim Inhibits Infection of Influenza a Virus in Chick Embryo","volume":"18","year":"2021","journal-title":"Virol. J."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wang, Z., Burwinkel, M., Chai, W., Lange, E., Blohm, U., Breithaupt, A., Hoffmann, B., Twardziok, S., Rieger, J., and Janczyk, P. (2014). Dietary Enterococcus Faecium Ncimb 10415 and Zinc Oxide Stimulate Immune Reactions to Trivalent Influenza Vaccination in Pigs but Do Not Affect Virological Response Upon Challenge Infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0087007"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"30317","DOI":"10.1021\/acsami.1c04412","article-title":"Zinc-Embedded Polyamide Fabrics Inactivate Sars-Cov-2 and Influenza a Virus","volume":"13","author":"Gopal","year":"2021","journal-title":"ACS Appl. Mater Interfaces"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1146\/annurev-nutr-122019-120635","article-title":"Dietary and Physiological Effects of Zinc on the Immune System","volume":"41","author":"Wessels","year":"2021","journal-title":"Annu. Rev. Nutr."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.autrev.2014.11.008","article-title":"Zinc and Its Role in Immunity and Inflammation","volume":"14","author":"Bonaventura","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"942","DOI":"10.3945\/ajcn.115.115188","article-title":"Effect of Zinc Supplementation on Serum Zinc Concentration and T Cell Proliferation in Nursing Home Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial","volume":"103","author":"Barnett","year":"2016","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jff.2018.07.027","article-title":"Influence of Zinc Deficiency and Supplementation on Nk Cell Cytotoxicity","volume":"48","author":"Rolles","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1002\/mnfr.201500524","article-title":"Zinc Supplementation Induces Regulatory T Cells by Inhibition of Sirt-1 Deacetylase in Mixed Lymphocyte Cultures","volume":"60","author":"Rosenkranz","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/s41385-020-0280-z","article-title":"Nmp4 Regulates the Innate Immune Response to Influenza a Virus Infection","volume":"14","author":"Yang","year":"2021","journal-title":"Mucosal. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e00842-17","DOI":"10.1128\/JVI.00842-17","article-title":"Zinc Finger-Containing Cellular Transcription Corepressor Zbtb25 Promotes Influenza Virus Rna Transcription and Is a Target for Zinc Ejector Drugs","volume":"91","author":"Chen","year":"2017","journal-title":"J. Virol."},{"key":"ref_65","first-page":"579","article-title":"Influenza a Virus Induced Apoptosis: Inhibition of DNA Laddering & Caspase-3 Activity by Zinc Supplementation in Cultured Hela Cells","volume":"129","author":"Srivastava","year":"2009","journal-title":"Indian J. Med. Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"15457","DOI":"10.1038\/s41598-020-72368-x","article-title":"Divalent Cation-Induced Conformational Changes of Influenza Virus Hemagglutinin","volume":"10","author":"Seok","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1021\/bi027176t","article-title":"Zinc- and Ph-Dependent Conformational Transition in a Putative Interdomain Linker Region of the Influenza Virus Matrix Protein M1","volume":"42","author":"Okada","year":"2003","journal-title":"Biochemistry"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/nature08722","article-title":"Structure of the Amantadine Binding Site of Influenza M2 Proton Channels in Lipid Bilayers","volume":"463","author":"Cady","year":"2010","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Puchkova, L.V., Kiseleva, I.V., Polishchuk, E.V., Broggini, M., and Ilyechova, E.Y. (2021). The Crossroads between Host Copper Metabolism and Influenza Infection. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115498"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1016\/j.bbrc.2014.06.037","article-title":"Alteration of Copper-Zinc Superoxide Dismutase 1 Expression by Influenza a Virus Is Correlated with Virus Replication","volume":"450","author":"Pyo","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s12985-016-0671-7","article-title":"Host Cell Copper Transporters Ctr1 and Atp7a Are Important for Influenza a Virus Replication","volume":"14","author":"Rupp","year":"2017","journal-title":"Virol. J."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115176","DOI":"10.1016\/j.diagmicrobio.2020.115176","article-title":"The Use of Copper to Help Prevent Transmission of Sars-Coronavirus and Influenza Viruses. A General Review","volume":"98","author":"Cortes","year":"2020","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0166-3542(98)00034-5","article-title":"Thujaplicin-Copper Chelates Inhibit Replication of Human Influenza Viruses","volume":"39","author":"Miyamoto","year":"1998","journal-title":"Antivir. Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1016\/j.arabjc.2020.06.021","article-title":"Two Cu(ii) Coordination Polymers: Photocatalytic Cr(Vi) Reduction and Treatment Activity on Influenza a Virus Infection by Inducing Ifitm Expression","volume":"13","author":"Chen","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s00705-008-0154-2","article-title":"Inactivation and Morphological Changes of Avian Influenza Virus by Copper Ions","volume":"153","author":"Horie","year":"2008","journal-title":"Arch. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1128\/AEM.01139-06","article-title":"Inactivation of Influenza a Virus on Copper Versus Stainless Steel Surfaces","volume":"73","author":"Noyce","year":"2007","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1074\/jbc.274.9.5474","article-title":"Cu(ii) Inhibition of the Proton Translocation Machinery of the Influenza a Virus M2 Protein","volume":"274","author":"Gandhi","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.bpj.2020.11.016","article-title":"Mechanism and Kinetics of Copper Complexes Binding to the Influenza a M2 S31n and S31n\/G34e Channels","volume":"120","author":"McGuire","year":"2021","journal-title":"Biophys. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"8693","DOI":"10.1021\/ja3026328","article-title":"Paramagnetic Cu(ii) for Probing Membrane Protein Structure and Function: Inhibition Mechanism of the Influenza M2 Proton Channel","volume":"134","author":"Su","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jhazmat.2016.03.023","article-title":"Comparison of the Antiviral Effect of Solid-State Copper and Silver Compounds","volume":"312","author":"Minoshima","year":"2016","journal-title":"J. Hazard Mater."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Ha, T., Pham, T.T.M., Kim, M., Kim, Y.H., Park, J.H., Seo, J.H., Kim, K.M., and Ha, E. (2022). Antiviral Activities of High Energy E-Beam Induced Copper Nanoparticles against H1n1 Influenza Virus. Nanomater, 12.","DOI":"10.3390\/nano12020268"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Das Jana, I., Kumbhakar, P., Banerjee, S., Gowda, C.C., Kedia, N., Kuila, S.K., Banerjee, S.K., Das, N.C., Das, A.K., and Manna, I. (2020). Development of a Copper-Graphene Nanocomposite Based Transparent Coating with Antiviral Activity against Influenza Virus. BioRxiv.","DOI":"10.1101\/2020.09.02.279737"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/0955-2863(90)90021-C","article-title":"Effects of Iron Deficiency Upon the Antibody Response to Influenza Virus in Rats","volume":"1","author":"Dhur","year":"1990","journal-title":"J. Nutr. Biochem."},{"key":"ref_84","first-page":"593","article-title":"Iron Status Is Linked to Disease Severity after Avian Influenza Virus H7n9 Infection","volume":"29","author":"Wang","year":"2020","journal-title":"Asia Pac. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1017\/S0022172400021215","article-title":"The Kinetics of Influenza-Virus Adsorption on Iron Oxide in the Process of Viral Purification and Concentration","volume":"69","author":"Larin","year":"1971","journal-title":"J. Hyg."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.jiac.2018.12.006","article-title":"Iron Oxide Nanoparticles Based Antiviral Activity of H1n1 Influenza a Virus","volume":"25","author":"Kumar","year":"2019","journal-title":"J. Infect. Chemother."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1002\/vms3.680","article-title":"Carboxymethyl Chitosan Bounded Iron Oxide Nanoparticles and Gamma-Irradiated Avian Influenza Subtype H9n2 Vaccine to Development of Immunity on Mouse and Chicken","volume":"8","author":"Saboorizadeh","year":"2022","journal-title":"Vet. Med. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6920","DOI":"10.7150\/thno.35826","article-title":"Catalytic Inactivation of Influenza Virus by Iron Oxide Nanozyme","volume":"9","author":"Qin","year":"2019","journal-title":"Theranostics"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.immuni.2018.03.017","article-title":"Manganese Increases the Sensitivity of the Cgas-Sting Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses","volume":"48","author":"Wang","year":"2018","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1038\/s41423-021-00669-w","article-title":"Manganese Salts Function as Potent Adjuvants","volume":"18","author":"Zhang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1128\/AAC.40.11.2626","article-title":"Inhibitory Effects of Recombinant Manganese Superoxide Dismutase on Influenza Virus Infections in Mice","volume":"40","author":"Sidwell","year":"1996","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Bantle, C.M., French, C.T., Cummings, J.E., Sadasivan, S., Tran, K., Slayden, R.A., Smeyne, R.J., and Tjalkens, R.B. (2021). Manganese Exposure in Juvenile C57bl\/6 Mice Increases Glial Inflammatory Responses in the Substantia Nigra Following Infection with H1n1 Influenza Virus. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245171"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kowalinski, E., Zubieta, C., Wolkerstorfer, A., Szolar, O.H., Ruigrok, R.W., and Cusack, S. (2012). Structural Analysis of Specific Metal Chelating Inhibitor Binding to the Endonuclease Domain of Influenza Ph1n1 (2009) Polymerase. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002831"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"DuBois, R.M., Slavish, P.J., Baughman, B.M., Yun, M.K., Bao, J., Webby, R.J., Webb, T.R., and White, S.W. (2012). Structural and Biochemical Basis for Development of Influenza Virus Inhibitors Targeting the Pa Endonuclease. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002830"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature07745","article-title":"The Cap-Snatching Endonuclease of Influenza Virus Polymerase Resides in the Pa Subunit","volume":"458","author":"Dias","year":"2009","journal-title":"Nature"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.3945\/jn.117.255901","article-title":"New Evidence against Chromium as an Essential Trace Element","volume":"147","author":"Vincent","year":"2017","journal-title":"J. Nutr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s40200-020-00501-8","article-title":"Chromium Supplementation; Negotiation with Diabetes Mellitus, Hyperlipidemia and Depression","volume":"19","author":"Khodavirdipour","year":"2020","journal-title":"J. Diabetes Metab. Disord."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1007\/s12011-018-1310-5","article-title":"A Review on the Role of Chromium Supplementation in Ruminant Nutrition-Effects on Productive Performance, Blood Metabolites, Antioxidant Status, and Immunocompetence","volume":"186","author":"Lashkari","year":"2018","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_99","first-page":"259","article-title":"Effects of Supplemental Chromium Picolinate and Chromium Nanoparticles on Performance and Antibody Titers of Infectious Bronchitis and Avian Influenza of Broiler Chickens under Heat Stress Condition","volume":"8","author":"Hajializadeh","year":"2017","journal-title":"Vet. Res. Forum."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1017\/S1751731118002379","article-title":"Dietary Supplementation of Organic or Inorganic Chromium Modulates the Immune Responses of Broilers Vaccinated with Avian Influenza Virus Vaccine","volume":"13","author":"Lu","year":"2019","journal-title":"Animal"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.freeradbiomed.2007.05.019","article-title":"Effect of Chromium Niacinate and Chromium Picolinate Supplementation on Lipid Peroxidation, Tnf-Alpha, Il-6, Crp, Glycated Hemoglobin, Triglycerides, and Cholesterol Levels in Blood of Streptozotocin-Treated Diabetic Rats","volume":"43","author":"Jain","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.anifeedsci.2010.06.004","article-title":"Effects of Supplemental Chromium Sources and Levels on Performance, Lipid Peroxidation and Proinflammatory Markers in Heat-Stressed Quails","volume":"159","author":"Sahin","year":"2010","journal-title":"Anim. Feed. Sci. Technol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"614000","DOI":"10.3389\/fimmu.2021.614000","article-title":"Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet","volume":"12","author":"Dworzanski","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.2527\/jas.2013-6932","article-title":"Effects of Temperature-Humidity Index and Chromium Supplementation on Antioxidant Capacity, Heat Shock Protein 72, and Cytokine Responses of Lactating Cows","volume":"92","author":"Zhang","year":"2014","journal-title":"J. Anim. Sci."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1080\/00071668.2012.747084","article-title":"Chromium Histidinate Protects against Heat Stress by Modulating the Expression of Hepatic Nuclear Transcription Factors in Quail","volume":"53","author":"Orhan","year":"2012","journal-title":"Br. Poult. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1016\/j.jhep.2018.01.003","article-title":"Hsp72 protects against liver injury via attenuation of hepatocellular death, oxidative stress, and JNK signaling","volume":"68","author":"Levada","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/nature07720","article-title":"Crystal Structure of an Avian Influenza Polymerase Pa(N) Reveals an Endonuclease Active Site","volume":"458","author":"Yuan","year":"2009","journal-title":"Nature"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9096","DOI":"10.1128\/JVI.00995-10","article-title":"Mutational and Metal Binding Analysis of the Endonuclease Domain of the Influenza Virus Polymerase Pa Subunit","volume":"84","author":"Crepin","year":"2010","journal-title":"J. Virol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1021\/jp408383g","article-title":"Magnesium-Dependent Rna Binding to the Pa Endonuclease Domain of the Avian Influenza Polymerase","volume":"118","author":"Xiao","year":"2014","journal-title":"J. Phys. Chem. B"},{"key":"ref_110","first-page":"R1","article-title":"Iodine: The Forgotten Weapon against Influenza Viruses","volume":"4","author":"Derry","year":"2009","journal-title":"Thyroid. Sci."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1007\/s12011-020-02334-1","article-title":"Multielement Determination in Medicinal Plants and Herbal Medicines Containing Cynara Scolymus L., Harpagophytum Procumbens D.C., and Maytenus Ilifolia (Mart.) Ex Reiss from Brazil Using Icp Oes","volume":"199","author":"Santana","year":"2021","journal-title":"Biol. Trace Elem. Res."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:16:26Z","timestamp":1760120186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/2\/184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,26]]},"references-count":111,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["metabo13020184"],"URL":"https:\/\/doi.org\/10.3390\/metabo13020184","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,26]]}}}