{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:59:37Z","timestamp":1787029177953,"version":"build-2736575974"},"reference-count":31,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["Grant Number JPMJOP1832, Japan."],"award-info":[{"award-number":["Grant Number JPMJOP1832, Japan."]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>It is difficult to match annual vaccines against the exact influenza strain that is spreading in any given flu season. Owing to the emergence of drug-resistant viral strains, new approaches for treating influenza are needed. Euglena gracilis (hereinafter Euglena), microalga, used as functional foods and supplements, have been shown to alleviate symptoms of influenza virus infection in mice. However, the mechanism underlying the inhibitory action of microalgae against the influenza virus is unknown. Here, we aimed to study the antiviral activity of Euglena extract against the influenza virus and the underlying action mechanism using Madin\u2013Darby canine kidney (MDCK) cells. Euglena extract strongly inhibited infection by all influenza virus strains examined, including those resistant to the anti-influenza drugs oseltamivir and amantadine. A time-of-addition assay revealed that Euglena extract did not affect the cycle of virus replication, and cell pretreatment or prolonged treatment of infected cells reduced the virus titer. Thus, Euglena extract may activate the host cell defense mechanisms, rather than directly acting on the influenza virus. Moreover, various minerals, mainly zinc, in Euglena extract were found to be involved in the antiviral activity of the extract. In conclusion, Euglena extract could be a potent agent for preventing and treating influenza.<\/jats:p>","DOI":"10.3390\/nu13113911","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:24:22Z","timestamp":1635805462000},"page":"3911","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Antiviral Activity and Underlying Action Mechanism of Euglena Extract against Influenza Virus"],"prefix":"10.3390","volume":"13","author":[{"given":"Ayaka","family":"Nakashima","sequence":"first","affiliation":[{"name":"Euglena Co., Ltd., Tokyo 108-0014, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Horio","sequence":"additional","affiliation":[{"name":"Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women\u2019s University, Nishinomiya 663-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Euglena Co., Ltd., Tokyo 108-0014, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9701-8431","authenticated-orcid":false,"given":"Yuji","family":"Isegawa","sequence":"additional","affiliation":[{"name":"Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women\u2019s University, Nishinomiya 663-8558, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/infdis\/159.3.430","article-title":"Resistance of influenza A virus to amantadine and rimantadine: Results of one decade of surveillance","volume":"159","author":"Belshe","year":"1989","journal-title":"J. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1126\/science.1187816","article-title":"Permissive secondary mutations enable the evolution of influenza oseltamivir resistance","volume":"328","author":"Bloom","year":"2010","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1038\/4371108a","article-title":"Avian flu: Isolation of drug resistant H5N1 influenza A virus","volume":"437","author":"Le","year":"2005","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1128\/JVI.00151-12","article-title":"Efficient transmission of pandemic H1N1 influenza viruses with high-level oseltamivir resistance","volume":"86","author":"Seibert","year":"2012","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1007\/978-3-319-54910-1_14","article-title":"Large-scale cultivation of Euglena","volume":"979","author":"Suzuki","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1292\/jvms.09-0526","article-title":"Oral administration of paramylon, a \u03b2-1,3-d-glucan isolated from Euglena gracilis Z inhibits development of atopic dermatitis-like skin lesions in NC\/Nga mice","volume":"72","author":"Sugiyama","year":"2010","journal-title":"J. Vet. Med. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Suzuki, K., Nakashima, A., Igarashi, M., Saito, K., Konno, M., Yamazaki, N., and Takimoto, H. (2018). Euglena gracilis Z and its carbohydrate storage substance relieve arthritis symptoms by modulating Th17 immunity. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0191462"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.bbrc.2017.09.167","article-title":"Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice","volume":"494","author":"Nakashima","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e0192404","DOI":"10.1371\/journal.pone.0192404","article-title":"Euglena extract suppresses adipocyte-differentiation in human adipose-derived stem cells","volume":"13","author":"Sugimoto","year":"2018","journal-title":"PLoS ONE"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"194812","DOI":"10.1155\/2014\/194812","article-title":"Tools and databases of the KOMICS web portal for preprocessing, mining, and dissemination of metabolomics data","volume":"2014","author":"Sakurai","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4360","DOI":"10.1021\/jf049613b","article-title":"Polyphenol screening of pomace from red and white grape varieties (Vitis vinifera L.) by HPLC-DAD-MS\/MS","volume":"52","author":"Kammerer","year":"2004","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1080\/09168451.2015.1045828","article-title":"Selection and characterization of Euglena anabaena var. minor as a new candidate Euglena species for industrial application","volume":"79","author":"Suzuki","year":"2015","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1002\/jsfa.8671","article-title":"Inhibition of influenza virus replication by adlay tea","volume":"98","author":"Nagai","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1128\/jcm.28.6.1308-1313.1990","article-title":"Rapid focus reduction neutralizations of influenza A and B viruses in microtiter system","volume":"28","author":"Okuno","year":"1990","journal-title":"J. Clin. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1128\/jvi.67.5.2552-2558.1993","article-title":"A common neutralizing epitope conserved between the hemagglutinins of influenza A virus H1 and H2 strains","volume":"67","author":"Okuno","year":"1993","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1128\/JCM.36.2.340-344.1998","article-title":"Application of subtype-specific monoclonal antibodies for rapid detection and identification of influenza A and B viruses","volume":"36","author":"Ueda","year":"1998","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0166-0934(99)00015-4","article-title":"Rapid detection and identification of two lineages of influenza B strains with monoclonal antibodies","volume":"79","author":"Nakagawa","year":"1999","journal-title":"J. Virol. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1177\/14.4.291","article-title":"The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: Ultrastructural cytochemistry by a new technique","volume":"14","author":"Graham","year":"1966","journal-title":"J. Histochem. Cytochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/s13238-010-0025-y","article-title":"Flu channel drug resistance: A tale of two sites","volume":"1","author":"Pielak","year":"2010","journal-title":"Protein Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/S1534-5807(03)00190-4","article-title":"Influenza B virus BM2 protein has ion channel activity that conducts protons across membranes","volume":"5","author":"Mould","year":"2003","journal-title":"Dev. Cell."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Te Velthuis, A.J., van den Worm, S.H., Sims, A.C., Baric, R.S., Snijder, E.J., and van Hemert, M.J. (2010). Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001176"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"70","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_24","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.antiviral.2006.08.002","article-title":"Increased adamantane resistance in influenza A(H3) viruses in Australia and neighbouring countries in 2005","volume":"73","author":"Barr","year":"2007","journal-title":"Antivir. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.chom.2010.05.008","article-title":"Cellular networks involved in the influenza virus life cycle","volume":"7","author":"Watanabe","year":"2010","journal-title":"Cell Host Microbe"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"9155","DOI":"10.1073\/pnas.1605146113","article-title":"Extracellular vesicles and viruses: Are they close relatives?","volume":"113","author":"Cremer","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3177\/jnsv.64.8","article-title":"\u03b2-Glucan in foods and its physiological functions","volume":"64","author":"Nakashima","year":"2018","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1271\/bbb.80503","article-title":"Carbohydrate binding specificity of recombinant human macrophage \u03b2-glucan receptor dectin-1","volume":"7","author":"Ujita","year":"2009","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"110166","DOI":"10.1016\/j.biopha.2020.110166","article-title":"Water extract from Euglena gracilis prevents lung carcinoma growth in mice by attenuation of the myeloid-derived cell population","volume":"127","author":"Ishiguro","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","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-activity relationship analysis","volume":"93","author":"Yang","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.cyto.2009.03.005","article-title":"Induction of type 1 interferon receptor by zinc in U937 cells","volume":"46","author":"Nagamine","year":"2009","journal-title":"Cytokine"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3911\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:23:42Z","timestamp":1760167422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/13\/11\/3911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,30]]},"references-count":31,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["nu13113911"],"URL":"https:\/\/doi.org\/10.3390\/nu13113911","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,30]]}}}