{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T14:06:12Z","timestamp":1779890772724,"version":"3.53.1"},"reference-count":88,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NRF of Korea","award":["2017R1A2B2010948"],"award-info":[{"award-number":["2017R1A2B2010948"]}]},{"name":"NRF of Korea","award":["2017R1A6A3A11032576"],"award-info":[{"award-number":["2017R1A6A3A11032576"]}]},{"name":"NRF of Korea","award":["2020R1C1C1009334"],"award-info":[{"award-number":["2020R1C1C1009334"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The use of vaccines is the most effective and reliable method for the prevention of viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after infection is necessary. Zanamivir was administered through inhalation for treatment of pandemic influenza A\/H1N1 in 2009. However, the emergence of drug-resistant strains can occur rapidly. Alloferon, an immunomodulatory drug developed as an NK cell activator, exerts antiviral effects against various viruses, particularly influenza viruses. Therefore, alloferon and zanamivir were administered in combination in an effort to improve the antiviral effect of zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of IL-6 and MIP-1\u03b1 in these cells and the activity of p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the antiviral efficacy of the alloferon\/zanamivir combination was performed. The results showed that combined treatment after infection with H1N1 prevented weight loss, increased the survival rate, and improved lung fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of p38 MAPK and c-Jun in lung tissue, which was increased by infection with H1N1. Therefore, the combination of alloferon\/zanamivir effectively prevents the development of H1N1-mediated inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.<\/jats:p>","DOI":"10.3390\/ijms24010678","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T04:07:09Z","timestamp":1672632429000},"page":"678","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection In Vitro and In Vivo"],"prefix":"10.3390","volume":"24","author":[{"given":"Dahae","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyejung","family":"Jo","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoojin","family":"Jang","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhyun","family":"Bae","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyo","family":"Agura","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Psychological and Brain Sciences, College of Arts and Sciences, Boston University, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Korea International School in Pangyo, Seongnam-si 13543, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-6397","authenticated-orcid":false,"given":"Nam-Hyuk","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Seoul National University Bundang Hospital, Seongnam-si 13620, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yejin","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul National University, Seoul 03080, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7675-9134","authenticated-orcid":false,"given":"Jae Seung","family":"Kang","sequence":"additional","affiliation":[{"name":"Laboratory of Vitamin C and Antioxidant Immunology, Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea"},{"name":"Medical Research Center, Institute of Allergy and Clinical Immunology, Seoul National University, Seoul 03080, Republic of 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