{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T14:23:26Z","timestamp":1789741406367,"version":"4.0.1"},"reference-count":31,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T00:00:00Z","timestamp":1465171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NRF funded by the MEST","award":["2010-0029242"],"award-info":[{"award-number":["2010-0029242"]}]},{"name":"Transgovernmental Enterprise for Pandemic Influenza","award":["A103001-1321"],"award-info":[{"award-number":["A103001-1321"]}]},{"DOI":"10.13039\/501100003624","name":"Ministry of Agriculture, Food and Rural Affairs","doi-asserted-by":"publisher","award":["114014-03-1-HD020"],"award-info":[{"award-number":["114014-03-1-HD020"]}],"id":[{"id":"10.13039\/501100003624","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB\/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles.<\/jats:p>","DOI":"10.3390\/v8060157","type":"journal-article","created":{"date-parts":[[2016,6,6]],"date-time":"2016-06-06T10:47:38Z","timestamp":1465210058000},"page":"157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection"],"prefix":"10.3390","volume":"8","author":[{"given":"Ji-Hye","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Duksung Women\u2019s University, Seoul 01369, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong","family":"Seok","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sella","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garam","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Duksung Women\u2019s University, Seoul 01369, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae-In","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Duksung Women\u2019s University, Seoul 01369, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Duksung Women\u2019s University, Seoul 01369, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Min","family":"Hong","sequence":"additional","affiliation":[{"name":"R &amp; D Center, Dong-il Shimadzu Corp., Seoul 08506, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Oh","family":"Kwon","sequence":"additional","affiliation":[{"name":"S &amp; D Co., Ltd., Osong, Cheongju, Chungbuk 28156, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Hun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Seon","family":"Song","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Konkuk University, Seoul 05029, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Mun","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Science, College of Health Science, Eulji University, Gyeonggi-do 13135, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition, Duksung Women\u2019s University, Seoul 01369, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioinformatics, Korea University, Sejong 30019, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1126\/science.1222213","article-title":"An overlapping protein-coding region in influenza A virus segment 3 modulates the host response","volume":"337","author":"Jagger","year":"2012","journal-title":"Science"},{"key":"ref_2","first-page":"17","article-title":"Optimizing antiviral therapy for influenza: Understanding the evidence","volume":"13","author":"Ison","year":"2015","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"966","DOI":"10.3201\/eid1506.081357","article-title":"Oseltamivir- and amantadine-resistant influenza viruses A (H1N1)","volume":"15","author":"Cheng","year":"2009","journal-title":"Emerg. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.bbrc.2013.08.090","article-title":"Aronia melanocarpa and its components demonstrate antiviral activity against influenza viruses","volume":"440","author":"Park","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1586\/14787210.2016.1120670","article-title":"The preventive and therapeutic potential of natural polyphenols on influenza","volume":"14","author":"Bahramsoltani","year":"2016","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_6","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_7","doi-asserted-by":"crossref","unstructured":"He, W., Han, H.M., Wang, W., and Gao, B. (2011). Anti-influenza virus effect of aqueous extracts from dandelion. Virol. J., 8.","DOI":"10.1186\/1743-422X-8-538"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.bbrc.2011.01.031","article-title":"High mannose-specific lectin (KAA-2) from the red alga Kappaphycus alvarezii potently inhibits influenza virus infection in a strain-independent manner","volume":"405","author":"Sato","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.antiviral.2012.04.001","article-title":"In vitro anti-influenza virus and anti-inflammatory activities of theaflavin derivatives","volume":"94","author":"Zu","year":"2012","journal-title":"Antivir. Res."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","first-page":"5121","DOI":"10.1021\/jf205350k","article-title":"Polyphenol compounds and anti-inflammatory activities of Korean black raspberry (Rubus coreanus Miquel) wines produced from juice supplemented with pulp and seed","volume":"60","author":"Lim","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0308-8146(03)00160-2","article-title":"Evaluation of the antioxidant properties of fruits","volume":"84","year":"2004","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.1016\/j.biortech.2007.08.063","article-title":"Antioxidant activities of ethanol extracts from seeds in fresh Bokbunja (Rubus coreanus Miq.) and wine processing waste","volume":"99","author":"Ku","year":"2008","journal-title":"Bioresour. Technol."},{"key":"ref_14","first-page":"367","article-title":"Lactic acid fermentation and biological activities of Rubus coreanus","volume":"46","author":"Park","year":"2003","journal-title":"J. Korean Soc. Agric. Chem. Biotechnol."},{"key":"ref_15","unstructured":"World Health Organization Manual for the Laboratory Diagnosis and Virological Surveillance of Influenza. Available online: http:\/\/apps.who.int\/iris\/bitstream\/10665\/44518\/1\/9789241548090_eng.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1055\/s-2002-32073","article-title":"Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay","volume":"68","author":"Bruggisser","year":"2002","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1128\/AAC.49.3.981-986.2005","article-title":"Mechanism of action of T-705 against influenza virus","volume":"49","author":"Furuta","year":"2005","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1099\/vir.0.051136-0","article-title":"Insight into structural diversity of influenza virus haemagglutinin","volume":"94","author":"Cho","year":"2013","journal-title":"J. Gen. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3568","DOI":"10.1128\/JVI.02238-08","article-title":"Amino acid residues in the fusion peptide pocket regulate the pH of activation of the H5N1 influenza virus hemagglutinin protein","volume":"83","author":"Reed","year":"2009","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Rajasekaran, D., Palombo, E.A., Yeo, T.C., Ley, D.L.S., Tu, C.L., Malherbe, F., and Grollo, L. (2013). Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0079293"},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1093\/glycob\/2.1.25","article-title":"Diversity in the sialic acids","volume":"2","author":"Varki","year":"1992","journal-title":"Glycobiology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/1471-2334-11-134","article-title":"Systematic review of influenza resistance to the neuraminidase inhibitors","volume":"11","author":"Thorlund","year":"2011","journal-title":"BMC Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3669","DOI":"10.1073\/pnas.1519772113","article-title":"Identification and characterization of influenza variants resistant to a viral endonuclease inhibitor","volume":"113","author":"Song","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Rowse, M., Qiu, S., Tsao, J., Xian, T., Khawaja, S., Yamauchi, Y., Yang, Z., Wang, G., and Luo, M. (2015). Characterization of potent fusion inhibitors of influenza virus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122536"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vigant, F., Lee, J., Hollmann, A., Tanner, L.B., Akyol Ataman, Z., Yun, T., Shui, G., Aguilar, H.C., Zhang, D., and Meriwether, D. (2013). A mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003297"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1016\/j.phymed.2009.06.002","article-title":"Pomegranate (Punica granatum) purified polyphenol extract inhibits influenza virus and has a synergistic effect with oseltamivir","volume":"16","author":"Haidari","year":"2009","journal-title":"Phytomedicine"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.3390\/v8010006","article-title":"Quercetin as an antiviral agent inhibits influenza A virus (IAV) entry","volume":"8","author":"Wu","year":"2016","journal-title":"Viruses"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Theisen, L.L., Erdelmeier, C.A., Spoden, G.A., Boukhallouk, F., Sausy, A., Florin, L., and Muller, C.P. (2014). Tannins from Hamamelis virginiana bark extract: Characterization and improvement of the antiviral efficacy against influenza A virus and human papillomavirus. PLoS ONE, 31.","DOI":"10.1371\/journal.pone.0088062"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2332","DOI":"10.1021\/jm980707k","article-title":"Potent inhibition of influenza sialidase by a benzoic acid containing a 2-pyrrolidinone substituent","volume":"13","author":"Atigadda","year":"1999","journal-title":"J. Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.antiviral.2016.01.011","article-title":"Antiviral activity of SA-2 against influenza A virus in vitro\/vivo and its inhibition of RNA polymerase","volume":"127","author":"Yu","year":"2016","journal-title":"Antivir. Res."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/6\/157\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:25:04Z","timestamp":1760210704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/6\/157"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,6]]},"references-count":31,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2016,6]]}},"alternative-id":["v8060157"],"URL":"https:\/\/doi.org\/10.3390\/v8060157","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,6]]}}}