{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:43:50Z","timestamp":1790696630239,"version":"4.1.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,12,16]],"date-time":"2023-12-16T00:00:00Z","timestamp":1702684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Government Department of Health and Age Care"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza antiviral drugs are important tools in our fight against both annual influenza epidemics and pandemics. Polyphenols are a group of compounds found in plants, some of which have demonstrated promising antiviral activity. Previous in vitro and mouse studies have outlined the anti-influenza virus effectiveness of the polyphenol epigallocatechin-3-gallate (EGCG); however, no study has utilised the ferret model, which is considered the gold-standard for influenza antiviral studies. This study aimed to explore the antiviral efficacy of EGCG in vitro and in ferrets. We first performed studies in Madin-Darby Canine Kidney (MDCK) and human lung carcinoma (Calu-3) cells, which demonstrated antiviral activity. In MDCK cells, we observed a selective index (SI, CC50\/IC50) of 77 (290 \u00b5M\/3.8 \u00b5M) and 96 (290 \u00b5M\/3.0 \u00b5M) against A\/California\/07\/2009 and A\/Victoria\/2570\/2019 (H1N1)pdm09 influenza virus, respectively. Calu-3 cells demonstrated a SI of 16 (420 \u00b5M\/26 \u00b5M) and 18 (420 \u00b5M\/24 \u00b5M). Ferrets infected with A\/California\/07\/2009 influenza virus and treated with EGCG (500 mg\/kg\/day for 4 days) had no change in respiratory tissue viral titres, in contrast to oseltamivir treatment, which significantly reduced viral load in the lungs of treated animals. Therefore, we demonstrated that although EGCG showed antiviral activity in vitro against influenza viruses, the drug failed to impair viral replication in the respiratory tract of ferrets.<\/jats:p>","DOI":"10.3390\/v15122447","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:41:35Z","timestamp":1702878095000},"page":"2447","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pre-Clinical Evaluation of the Antiviral Activity of Epigalocatechin-3-Gallate, a Component of Green Tea, against Influenza A(H1N1)pdm Viruses"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9748-7668","authenticated-orcid":false,"given":"Harry","family":"Stannard","sequence":"first","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Koszalka","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Deshpande","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0398-2797","authenticated-orcid":false,"given":"Yves","family":"Desjardins","sequence":"additional","affiliation":[{"name":"Institute of Nutrition and Functional Foods, Centre Nutrition, Sant\u00e9 et Societ\u00e9 (NUTRISS) Center, Facult\u00e9 de Sciences de L\u2019agriculture et de L\u2019alimentation (FSAA), Universit\u00e9 Laval, Quebec City, QC G1V 4L3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-0735","authenticated-orcid":false,"given":"Mariana","family":"Baz","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre for Reference and Research on Influenza, at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia"},{"name":"Department of Microbiology and Immunology, at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: A modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_2","unstructured":"WHO (2023, January 25). 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_3","doi-asserted-by":"crossref","first-page":"e01056-22","DOI":"10.1128\/mbio.01056-22","article-title":"Effect of Baloxavir and Oseltamivir in Combination on Infection with Influenza Viruses with PA\/I38T or PA\/E23K Substitutions in the Ferret Model","volume":"13","author":"Koszalka","year":"2022","journal-title":"Mbio"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"114189","DOI":"10.1016\/j.ejmech.2022.114189","article-title":"Influenza-existing drugs and treatment prospects","volume":"232","author":"Sarker","year":"2022","journal-title":"Eur. J. Med. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"317S","DOI":"10.1093\/ajcn\/81.1.317S","article-title":"Polyphenols and disease risk in epidemiologic studies","volume":"81","author":"Arts","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3389\/fphar.2022.806470","article-title":"Dietary Polyphenols and Their Role in Oxidative Stress-Induced Human Diseases: Insights Into Protective Effects, Antioxidant Potentials and Mechanism(s) of Action","volume":"13","author":"Rudrapal","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3389\/fnut.2018.00087","article-title":"The Role of Polyphenols in Human Health and Food Systems: A Mini-Review","volume":"5","author":"Cory","year":"2018","journal-title":"Front. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Trisha, A.T., Shakil, M.H., Talukdar, S., Rovina, K., Huda, N., and Zzaman, W. (2022). Tea Polyphenols and Their Preventive Measures against Cancer: Current Trends and Directions. Foods, 11.","DOI":"10.3390\/foods11213349"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yang, C.S., and Wang, H. (2016). Cancer Preventive Activities of Tea Catechins. Molecules, 21.","DOI":"10.3390\/molecules21121679"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Musial, C., Kuban-Jankowska, A., and Gorska-Ponikowska, M. (2020). Beneficial Properties of Green Tea Catechins. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21051744"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.antiviral.2013.08.002","article-title":"Inhibition of influenza virus internalization by (-)-epigallocatechin-3-gallate","volume":"100","author":"Kim","year":"2013","journal-title":"Antivir. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.antiviral.2005.06.010","article-title":"Antiviral effect of catechins in green tea on influenza virus","volume":"68","author":"Song","year":"2005","journal-title":"Antivir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"103894","DOI":"10.1016\/j.jff.2020.103894","article-title":"Green tea catechins adsorbed on the murine pharyngeal mucosa reduce influenza A virus infection","volume":"68","author":"Onishi","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Matsuura, R., Kawamura, A., Matsumoto, Y., Iida, Y., Kanayama, M., Kurokawa, M., and Aida, Y. (2022). Epigallocatechin Gallate Stabilized by Cyclodextrin Inactivates Influenza Virus and Human Coronavirus 229E. Microorganisms, 10.","DOI":"10.3390\/microorganisms10091796"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1038\/aps.2012.80","article-title":"Amelioration of influenza virus-induced reactive oxygen species formation by epigallocatechin gallate derived from green tea","volume":"33","author":"Ling","year":"2012","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7806","DOI":"10.1128\/JVI.00896-14","article-title":"A small molecule inhibits virion attachment to heparan sulfate- or sialic acid-containing glycans","volume":"88","author":"Colpitts","year":"2014","journal-title":"J. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Ohishi, T., Hishiki, T., Baig, M.S., Rajpoot, S., Saqib, U., Takasaki, T., and Hara, Y. (2022). Epigallocatechin gallate (EGCG) attenuates severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection by blocking the interaction of SARS-CoV-2 spike protein receptor-binding domain to human angiotensin-converting enzyme 2. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0271112"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12899","DOI":"10.1038\/s41598-022-17088-0","article-title":"The green tea catechin EGCG provides proof-of-concept for a pan-coronavirus attachment inhibitor","volume":"12","author":"LeBlanc","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"956113","DOI":"10.3389\/fviro.2022.956113","article-title":"Epigallocatechin Gallate and Isoquercetin Synergize With Remdesivir to Reduce SARS-CoV-2 Replication In Vitro","volume":"2","author":"Rabezanahary","year":"2022","journal-title":"Front. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liu, J., Bodnar, B.H., Meng, F., Khan, A.I., Wang, X., Saribas, S., Wang, T., Lohani, S.C., Wang, P., and Wei, Z. (2021). Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor. Cell Biosci., 11.","DOI":"10.1186\/s13578-021-00680-8"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/hep.24610","article-title":"The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry","volume":"54","author":"Ciesek","year":"2011","journal-title":"Hepatology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/hep.24803","article-title":"(\u2212)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry","volume":"55","author":"Calland","year":"2012","journal-title":"Hepatology"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lee, Y.H., Jang, Y.H., Byun, Y.H., Cheong, Y., Kim, P., Lee, Y.J., Lee, Y.J., Sung, J.M., Son, A., and Lee, H.M. (2017). Green Tea Catechin-Inactivated Viral Vaccine Platform. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02469"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1086\/430954","article-title":"Influenza Virus Neuraminidase Contributes to Secondary Bacterial Pneumonia","volume":"192","author":"Peltola","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rawangkan, A., Kengkla, K., Kanchanasurakit, S., Duangjai, A., and Saokaew, S. (2021). Anti-Influenza with Green Tea Catechins: A Systematic Review and Meta-Analysis. Molecules, 26.","DOI":"10.3390\/molecules26134014"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1007\/s00394-021-02681-2","article-title":"Preventive effects of tea and tea catechins against influenza and acute upper respiratory tract infections: A systematic review and meta-analysis","volume":"60","author":"Umeda","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Furushima, D., Nishimura, T., Takuma, N., Iketani, R., Mizuno, T., Matsui, Y., Yamaguchi, T., Nakashima, Y., Yamamoto, S., and Hibi, M. (2020). Prevention of Acute Upper Respiratory Infections by Consumption of Catechins in Healthcare Workers: A Randomized, Placebo-Controlled Trial. Nutrients, 12.","DOI":"10.3390\/nu12010004"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Matsumoto, K., Yamada, H., Takuma, N., Niino, H., and Sagesaka, Y.M. (2011). Effects of green tea catechins and theanine on preventing influenza infection among healthcare workers: A randomized controlled trial. BMC Complement. Altern. Med., 11.","DOI":"10.1186\/1472-6882-11-15"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.intimp.2017.08.023","article-title":"Epigallocatechin-3-gallate inhibits TLR4 signaling through the 67-kDa laminin receptor and effectively alleviates acute lung injury induced by H9N2 swine influenza virus","volume":"52","author":"Xu","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"a038323","DOI":"10.1101\/cshperspect.a038323","article-title":"Ferreting Out Influenza Virus Pathogenicity and Transmissibility: Past and Future Risk Assessments in the Ferret Model","volume":"10","author":"Belser","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Stannard, H.L., Mifsud, E.J., Wildum, S., Brown, S.K., Koszalka, P., Shishido, T., Kojima, S., Omoto, S., Baba, K., and Kuhlbusch, K. (2022). Assessing the fitness of a dual-antiviral drug resistant human influenza virus in the ferret model. Commun. Biol., 5.","DOI":"10.1038\/s42003-022-04005-4"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.antiviral.2019.02.007","article-title":"Baloxavir marboxil susceptibility of influenza viruses from the Asia-Pacific, 2012\u20132018","volume":"164","author":"Koszalka","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Oh, D.Y., Barr, I.G., and Hurt, A.C. (2015). A Novel Video Tracking Method to Evaluate the Effect of Influenza Infection and Antiviral Treatment on Ferret Activity. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0118780"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Epidemiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"66","DOI":"10.3382\/ps.2011-01645","article-title":"Anti-influenza virus activity of green tea by-products in vitro and efficacy against influenza virus infection in chickens","volume":"91","author":"Lee","year":"2012","journal-title":"Poult. Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1177\/147323000303100205","article-title":"A single ascending dose study of epigallocatechin gallate in healthy volunteers","volume":"31","author":"Ullmann","year":"2003","journal-title":"J. Int. Med. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"373","DOI":"10.3390\/antiox4020373","article-title":"Food Inhibits the Oral Bioavailability of the Major Green Tea Antioxidant Epigallocatechin Gallate in Humans","volume":"4","author":"Naumovski","year":"2015","journal-title":"Antioxidants"},{"key":"ref_38","first-page":"105","article-title":"Pharmacokinetic and chemoprevention studies on tea in humans","volume":"64","author":"Chow","year":"2011","journal-title":"Pharmacol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/19390210802414279","article-title":"Pharmacokinetics of green tea catechins in extract and sustained-release preparations","volume":"5","author":"Janle","year":"2008","journal-title":"J. Diet. Suppl."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.antiviral.2011.02.014","article-title":"A comparison of pyrosequencing and neuraminidase inhibition assays for the detection of oseltamivir-resistant pandemic influenza A(H1N1) 2009 viruses","volume":"90","author":"Deng","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1136\/vr.100628","article-title":"Reference ranges for laboratory parameters in ferrets","volume":"171","author":"Hein","year":"2012","journal-title":"Vet. Rec."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.fitote.2013.12.011","article-title":"Comparison of in vitro antiviral activity of tea polyphenols against influenza A and B viruses and structure\u2013activity relationship analysis","volume":"93","author":"Yang","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Furubayashi, T., Inoue, D., Nishiyama, N., Tanaka, A., Yutani, R., Kimura, S., Katsumi, H., Yamamoto, A., and Sakane, T. (2020). Comparison of Various Cell Lines and Three-Dimensional Mucociliary Tissue Model Systems to Estimate Drug Permeability Using an In Vitro Transport Study to Predict Nasal Drug Absorption in Rats. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010079"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1165\/rcmb.2010-0157OC","article-title":"Human influenza is more effective than avian influenza at antiviral suppression in airway cells","volume":"44","author":"Hsu","year":"2011","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1023\/B:PHAM.0000033013.45204.c3","article-title":"Cellular Uptake But Low Permeation of Human Calcitonin-Derived Cell Penetrating Peptides and Tat(47-57) Through Well-Differentiated Epithelial Models","volume":"21","author":"Krauss","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Marriott, A.C., Dove, B.K., Whittaker, C.J., Bruce, C., Ryan, K.A., Bean, T.J., Rayner, E., Pearson, G., Taylor, I., and Dowall, S. (2014). Low Dose Influenza Virus Challenge in the Ferret Leads to Increased Virus Shedding and Greater Sensitivity to Oseltamivir. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0094090"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.antiviral.2011.05.008","article-title":"Assessment of the efficacy of the neuraminidase inhibitor oseltamivir against 2009 pandemic H1N1 influenza virus in ferrets","volume":"91","author":"Govorkova","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"104751","DOI":"10.1016\/j.antiviral.2020.104751","article-title":"Prophylaxis of ferrets with nitazoxanide and oseltamivir combinations is more effective at reducing the impact of influenza a virus infection compared to oseltamivir monotherapy","volume":"176","author":"Mifsud","year":"2020","journal-title":"Antivir. Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Mok, C.-K., Ng, Y.L., Ahidjo, B.A., Aw, Z.Q., Chen, H., Wong, Y.H., Lee, R.C.H., Loe, M.W.C., Liu, J., and Tan, K.S. (2023). Evaluation of In Vitro and In Vivo Antiviral Activities of Vitamin D for SARS-CoV-2 and Variants. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15030925"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.3390\/ijms12095592","article-title":"Epigallocatechin-3-gallate (EGCG) for clinical trials: More pitfalls than promises?","volume":"12","author":"Mereles","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1182\/blood-2006-05-022814","article-title":"Specific killing of multiple myeloma cells by (-)-epigallocatechin-3-gallate extracted from green tea: Biologic activity and therapeutic implications","volume":"108","author":"Shammas","year":"2006","journal-title":"Blood"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5365","DOI":"10.1021\/acs.jafc.7b01707","article-title":"Bioavailability of Black Tea Theaflavins: Absorption, Metabolism, and Colonic Catabolism","volume":"65","author":"Brindani","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"175332","DOI":"10.1016\/j.ejphar.2022.175332","article-title":"Anti-inflammatory effects of theaflavin-3\u2032-gallate during influenza virus infection through regulating the TLR4\/MAPK\/p38 pathway","volume":"938","author":"Sima","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/j.carbpol.2016.05.113","article-title":"Enhancement of antioxidant activity of green tea epicatechins in \u03b2-cyclodextrin cavity: Single-crystal X-ray analysis, DFT calculation and DPPH assay","volume":"151","author":"Aree","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1124\/dmd.31.5.572","article-title":"Enzymology of methylation of tea catechins and inhibition of catechol-O-methyltransferase by (\u2212)-epigallocatechin gallate","volume":"31","author":"Lu","year":"2003","journal-title":"Drug Metab. Dispos. Biol. Fate Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.fct.2005.11.003","article-title":"Safety studies on epigallocatechin gallate (EGCG) preparations. Part 2: Dermal, acute and short-term toxicity studies","volume":"44","author":"Isbrucker","year":"2006","journal-title":"Food Chem. Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1177\/0192623310382437","article-title":"Fourteen-week toxicity study of green tea extract in rats and mice","volume":"38","author":"Chan","year":"2010","journal-title":"Toxicol. Pathol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1242\/dmm.007823","article-title":"The ferret as a model organism to study influenza A virus infection","volume":"4","author":"Belser","year":"2011","journal-title":"Dis. Models Mech."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1128\/MMBR.00022-16","article-title":"Complexities in Ferret Influenza Virus Pathogenesis and Transmission Models","volume":"80","author":"Belser","year":"2016","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"769088","DOI":"10.3389\/fimmu.2021.769088","article-title":"Epigallocatechin-3-Gallate as a Novel Vaccine Adjuvant","volume":"12","author":"Cheong","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"23101","DOI":"10.1038\/s41598-021-02346-4","article-title":"Methylated (\u2212)-epigallocatechin 3-O-gallate potentiates the effect of split vaccine accompanied with upregulation of Toll-like receptor 5","volume":"11","author":"Kumazoe","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2447\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:40:10Z","timestamp":1760132410000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2447"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,16]]},"references-count":61,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["v15122447"],"URL":"https:\/\/doi.org\/10.3390\/v15122447","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,16]]}}}