{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:54:47Z","timestamp":1785412487418,"version":"3.56.0"},"reference-count":33,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Health of the Russian Federation","award":["125040704919-6"],"award-info":[{"award-number":["125040704919-6"]}]},{"award":["125040704919-6"],"award-info":[{"award-number":["125040704919-6"]}],"id":[{"id":"https:\/\/ror.org\/01p8ehb87","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Viral infections remain a global public health challenge. Stimulating the innate immune system is a potent therapeutic strategy that promotes pathogen clearance, directly impacting disease severity and clinical outcomes. Interferons and interferon-stimulated genes (ISGs) are critical components of this antiviral defense system. Neomycin, an aminoglycoside antibiotic, can induce ISG expression and help establish an antiviral state. In this study, we demonstrated that neomycin induces the production of pro-inflammatory cytokines (IL1\u03b2, TNF\u03b1, IL6, GM-CSF, and IFN-\u03b3) in peripheral mononuclear blood cells (PBMCs) and activates key antiviral ISGs, including MxA, OAS1, and IRF7. The protein expression profiles elicited by neomycin were comparable to those induced by poly(I:C). Intranasal delivery of neomycin to CBA and BALB\/c mice induced various ISGs in both the respiratory tract and splenic tissues. Prophylactic administration of neomycin significantly inhibited influenza B virus replication in the lung and nasal turbinates of CBA mice in a sublethal infection model. Overall, our data suggest that neomycin, when used prophylactically alone or combined with other antiviral strategies, shows considerable potential for the attenuation of influenza B virus infections.<\/jats:p>","DOI":"10.3390\/v18040444","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:03:47Z","timestamp":1775563427000},"page":"444","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neomycin Exhibits Immunomodulatory and Antiviral Activity Against Influenza B Virus"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-398X","authenticated-orcid":false,"given":"Ekaterina","family":"Romanovskaya-Romanko","sequence":"first","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-3156","authenticated-orcid":false,"given":"Marina","family":"Plotnikova","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3685-7068","authenticated-orcid":false,"given":"Anna-Polina","family":"Shurygina","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7550-5519","authenticated-orcid":false,"given":"Marina","family":"Shuklina","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-6560","authenticated-orcid":false,"given":"Sergey","family":"Klotchenko","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanna","family":"Buzitskaya","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry","family":"Lioznov","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Stukova","sequence":"additional","affiliation":[{"name":"Smorodintsev Research Institute of Influenza, Ministry of Health of the Russian Federation, Saint-Petersburg 197022, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100986","DOI":"10.1016\/j.eclinm.2021.100986","article-title":"Global burden of upper respiratory infections in 204 countries and territories, from 1990 to 2019","volume":"37","author":"Jin","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e017271","DOI":"10.1136\/bmjgh-2024-017271","article-title":"Seasonal influenza surveillance and vaccination policies in the WHO South-East Asian Region","volume":"10","author":"Haider","year":"2025","journal-title":"BMJ Glob. Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/CMR.00102-15","article-title":"Approved antiviral drugs over the past 50 years","volume":"29","author":"Li","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"83","DOI":"10.20953\/1817-7646-2021-4-83-97","article-title":"Impact of immunomodulation therapy on the course of acute viral respiratory infections: A meta-analysis of clinical trials assessing the efficacy and safety of ergoferon in the treatment of influenza and other acute respiratory viral infections","volume":"16","author":"Gorelov","year":"2021","journal-title":"Vopr. Prakt. Pediatr."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Strzelec, M., Detka, J., Mieszczak, P., Soboci\u0144ska, M.K., and Majka, M. (2023). Immunomodulation\u2014A general review of the current state-of-the-art and new therapeutic strategies for targeting the immune system. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1127704"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1038\/s41556-025-01692-z","article-title":"P4-ATPases control phosphoinositide membrane asymmetry and neomycin resistance","volume":"27","author":"Jain","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, S., Woo, J.H., Jun, S.H., Moon, D.C., Lim, S.-K., and Lee, J.C. (2020). Synergy between Florfenicol and Aminoglycosides against Multidrug-Resistant Escherichia coli Isolates from Livestock. Antibiotics, 9.","DOI":"10.3390\/antibiotics9040185"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2319566121","DOI":"10.1073\/pnas.2319566121","article-title":"Intranasal neomycin evokes broad-spectrum antiviral immunity in the upper respiratory tract","volume":"121","author":"Mao","year":"2024","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","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_10","doi-asserted-by":"crossref","unstructured":"Yu, Y.-R.A., O\u2019Koren, E.G., Hotten, D.F., Kan, M.J., Kopin, D., Nelson, E.R., Que, L., and Gunn, M.D. (2016). A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0150606"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41564-018-0138-2","article-title":"Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner","volume":"3","author":"Gopinath","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11311","DOI":"10.1073\/pnas.172195399","article-title":"A nonsense mutation in the gene encoding is associated with West Nile virus susceptibility in laboratory mice","volume":"99","author":"Mashimo","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","first-page":"89","article-title":"Generation of congenic mouse strains by introducing the virus-resistant genes, Mx1 and Oas1b, of feral mouse-derived inbred strain MSM\/Ms into the common strain C57BL\/6J","volume":"57","author":"Moritoh","year":"2009","journal-title":"Jpn. J. Vet. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1016\/S0140-6736(11)61051-9","article-title":"Global burden of respiratory infections due to seasonal influenza in young children: A systematic review and meta-analysis","volume":"378","author":"Nair","year":"2011","journal-title":"Lancet"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1586\/eri.11.56","article-title":"Immunomodulatory therapy for severe influenza","volume":"9","author":"Darwish","year":"2011","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bawage, S.S., Tiwari, P.M., Pillai, S., Dennis, V.A., and Singh, S.R. (2019). Antibiotic minocycline prevents respiratory syncytial virus infection. Viruses, 11.","DOI":"10.3390\/v11080739"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"65","DOI":"10.17816\/MAJ623374","article-title":"Comparative Analysis of Mxa, Oas1, Pkr Gene Expression Levels in Leukocytes of Patients With Influenza and Coronavirus Infection","volume":"23","author":"Klotchenko","year":"2023","journal-title":"Med. Acad. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yang, E., and Li, M.M.H. (2020). All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.605024"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1038\/s41467-018-05489-7","article-title":"T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory CD4 T cells","volume":"9","author":"Jain","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6876","DOI":"10.1038\/s41467-022-34602-0","article-title":"TLR3 forms a highly organized cluster when bound to a poly(I:C) RNA ligand","volume":"13","author":"Lim","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1038\/s41556-025-01707-9","article-title":"Phosphoinositide flipping governs neomycin sensitivity","volume":"27","author":"Salsaa","year":"2025","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0264-410X(00)00275-9","article-title":"Inflammatory responses in influenza A virus infection","volume":"19","author":"Julkunen","year":"2000","journal-title":"Vaccine"},{"key":"ref_23","first-page":"4518","article-title":"Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation","volume":"8","author":"Staeheli","year":"1988","journal-title":"Mol. Cell. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10818","DOI":"10.1128\/JVI.01116-07","article-title":"The Mx1 Gene Protects Mice against the Pandemic 1918 and Highly Lethal Human H5N1 Influenza Viruses","volume":"81","author":"Tumpey","year":"2007","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cell.2015.01.040","article-title":"A serpin shapes the extracellular environment to prevent influenza a virus maturation","volume":"160","author":"Dittmann","year":"2015","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Hamamoto, I., Takaku, H., Tashiro, M., and Yamamoto, N. (2013). High Yield Production of Influenza Virus in Madin Darby Canine Kidney (MDCK) Cells with Stable Knockdown of IRF7. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0059892"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1246980","DOI":"10.1126\/science.1246980","article-title":"Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells","volume":"343","author":"Lee","year":"2014","journal-title":"Science"},{"key":"ref_28","first-page":"109","article-title":"Host genetics of severe influenza: From mouse Mx1 to human IRF7","volume":"38","author":"Ciancanellia","year":"2016","journal-title":"Physiol. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1126\/science.1093616","article-title":"Innate Antiviral Responses by Means of TLR7-Mediated Recognition of Single-Stranded RNA","volume":"303","author":"Diebold","year":"2004","journal-title":"Science"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e0121723","DOI":"10.1128\/jvi.01217-23","article-title":"OAS1 suppresses African swine fever virus replication by recruiting TRIM21 to degrade viral major capsid protein","volume":"97","author":"Sun","year":"2023","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"133","DOI":"10.5483\/BMBRep.2019.52.2.129","article-title":"OAS1 and OAS3 negatively regulate the expression of chemokines and interferon-responsive genes in human macrophages","volume":"52","author":"Lee","year":"2019","journal-title":"BMB Rep."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Zhang, H., Floyd, K., Fang, Z., Hoffmann, F.A., Lee, A., Froggatt, H.M., Bharj, G., Xie, X., Eppler, H.B., and Santagata, J.M. (2026). Mucosal vaccination in mice provides protection from diverse respiratory threats. Science, eaea1260.","DOI":"10.1126\/science.aea1260"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1007\/s00018-025-05611-1","article-title":"Antiviral strategies against influenza virus: An update on approved and innovative therapeutic approaches","volume":"82","author":"Bonomini","year":"2025","journal-title":"Cell. Mol. Life Sci."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/444\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:07:31Z","timestamp":1775563651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/4\/444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,7]]},"references-count":33,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["v18040444"],"URL":"https:\/\/doi.org\/10.3390\/v18040444","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,7]]}}}