{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:54:43Z","timestamp":1790726083361,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Coronavirus Disease 2019 (COVID-19) pandemic and the subsequent increase in respiratory viral infections highlight the need for broad-spectrum antivirals to enable a quick and efficient reaction to current and emerging viral outbreaks. We previously demonstrated that the antihistamine azelastine hydrochloride (azelastine-HCl) exhibited in vitro antiviral activity against SARS-CoV-2. Furthermore, in a phase 2 clinical study, a commercial azelastine-containing nasal spray significantly reduced the viral load in SARS-CoV-2-infected individuals. Here, we evaluate the efficacy of azelastine-HCl against additional human coronaviruses, including the SARS-CoV-2 omicron variant and a seasonal human coronavirus, 229E, through in vitro infection assays, with azelastine showing a comparable potency against both. Furthermore, we determined that azelastine-HCl also inhibits the replication of Respiratory syncytial virus A (RSV A) in both prophylactic and therapeutic settings. In a human 3D nasal tissue model (MucilAirTM-Pool, Epithelix), azelastine-HCl protected tissue integrity and function from the effects of infection with influenza A H1N1 and resulted in a reduced viral load soon after infection. Our results suggest that azelastine-HCl has a broad antiviral effect and can be considered a safe option against the most common respiratory viruses to prevent or treat such infections locally in the form of a nasal spray that is commonly available globally.<\/jats:p>","DOI":"10.3390\/v15122300","type":"journal-article","created":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T11:31:25Z","timestamp":1700739085000},"page":"2300","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antiviral Potential of Azelastine against Major Respiratory Viruses"],"prefix":"10.3390","volume":"15","author":[{"given":"Katrin","family":"Fischhuber","sequence":"first","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3826-5800","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"B\u00e1nki","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7905","authenticated-orcid":false,"given":"Janine","family":"Kimpel","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Kragl","sequence":"additional","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5298-0288","authenticated-orcid":false,"given":"Annika","family":"R\u00f6ssler","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Bolze","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Muellauer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Angerer","sequence":"additional","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e1bor","family":"Nagy","sequence":"additional","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eszter","family":"Nagy","sequence":"additional","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Szijarto","sequence":"additional","affiliation":[{"name":"CEBINA GmbH, 1030 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6014","DOI":"10.1136\/bmjgh-2021-006014","article-title":"Global Hospital Admissions and In-Hospital Mortality Associated with All-cause and virus-Specific acute Lower Respiratory Infections in Children and Adolescents Aged 5\u201319 Years between 1995 and 2019: A Systematic Review and Modelling Study","volume":"6","author":"Wang","year":"2021","journal-title":"BMJ Glob. Health"},{"key":"ref_2","unstructured":"(2018). Estimates of the Global, Regional, and National Morbidity, Mortality, and Aetiologies of Lower Respiratory Infections in 195 Countries, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Infect. Dis., 18, 1191\u20131210."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1177\/00333549101250S305","article-title":"Influenza: The Once and Future Pandemic","volume":"125","author":"Taubenberger","year":"2010","journal-title":"Public Health Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gray, G.C., Robie, E.R., Studstill, C.J., and Nunn, C.L. (2021). Mitigating Future Respiratory Virus Pandemics: New Threats and Approaches to Consider. Viruses, 13.","DOI":"10.3390\/v13040637"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/s43440-023-00463-7","article-title":"Nasal Sprays for Treating COVID-19: A Scientific Note The Post-COVID Era-Advances and Challenges In","volume":"75","author":"Chavda","year":"2023","journal-title":"Pharmacol. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Li, L., Wei, Y., Yang, H., Yan, J., Li, X., Li, Z., Zhao, Y., Liang, H., and Wang, H. (2022). Advances in Next-Generation Coronavirus Vaccines in Response to Future Virus Evolution. Vaccines, 10.","DOI":"10.3390\/vaccines10122035"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1146\/annurev-biodatasci-020722-041304","article-title":"Challenges and Progress in Designing Broad-Spectrum Vaccines Against Rapidly Mutating Viruses","volume":"6","author":"Bedi","year":"2023","journal-title":"Annu. Rev. Biomed. Data Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e170236","DOI":"10.1172\/JCI170236","article-title":"Preparing for the Next Viral Threat with Broad-Spectrum Antivirals","volume":"133","author":"Karim","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"W272","DOI":"10.1093\/nar\/gkac348","article-title":"DrugVirus.Info 2.0: An Integrative Data Portal for Broad-Spectrum Antivirals (BSA) and BSA-Containing Drug Combinations (BCCs)","volume":"50","author":"Ianevski","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.ijid.2020.02.018","article-title":"Discovery and Development of Safe-in-Man Broad-Spectrum Antiviral Agents","volume":"93","author":"Andersen","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6839","DOI":"10.1038\/s41598-023-32546-z","article-title":"Early Intervention with Azelastine Nasal Spray May Reduce Viral Load in SARS-CoV-2 Infected Patients","volume":"13","author":"Klussmann","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Garcia-Blanco, M.A., Ooi, E.E., and Sessions, O.M. (2022). RNA Viruses, Pandemics and Anticipatory Preparedness. Viruses, 14.","DOI":"10.3390\/v14102176"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7271","DOI":"10.1016\/j.vaccine.2007.07.025","article-title":"Immunogenicity and Efficacy of Codon Optimized DNA Vaccines Encoding the F-Protein of Respiratory Syncytial Virus","volume":"25","author":"Ternette","year":"2007","journal-title":"Vaccine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1016\/j.jaci.2017.07.018","article-title":"Propagation of Respiratory Viruses in Human Airway Epithelia Reveals Persistent Virus-Specific Signatures","volume":"141","author":"Brito","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Riepler, L., R\u00f6ssler, A., Falch, A., Volland, A., Borena, W., Kimpel, J., and von Laer, D. (2021). Comparison of Four SARS-CoV-2 Neutralization Assays. Vaccines, 9.","DOI":"10.3390\/vaccines9010013"},{"key":"ref_16","unstructured":"Kapetanovic, I.M. (2011). Drug Discovery and Development, IntechOpen."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/0042-6822(89)90050-0","article-title":"Sequence Analysis of the Nucleocapsid Protein Gene of Human Coronavirus 229E","volume":"169","author":"Schreiber","year":"1989","journal-title":"Virology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"861295","DOI":"10.3389\/fphar.2022.861295","article-title":"The Anti-Histamine Azelastine, Identified by Computational Drug Repurposing, Inhibits Infection by Major Variants of SARS-CoV-2 in Cell Cultures and Reconstituted Human Nasal Tissue","volume":"13","author":"Konrat","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1038\/s41591-022-01753-y","article-title":"Effectiveness of MRNA-1273 against SARS-CoV-2 Omicron and Delta Variants","volume":"28","author":"Ackerson","year":"2022","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41586-021-04387-1","article-title":"Omicron Extensively but Incompletely Escapes Pfizer BNT162b2 Neutralization","volume":"602","author":"Cele","year":"2022","journal-title":"Nature"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1038\/s41564-022-01143-7","article-title":"SARS-CoV-2 Omicron Is an Immune Escape Variant with an Altered Cell Entry Pathway","volume":"7","author":"Willett","year":"2022","journal-title":"Nat. Microbiol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Akerman, A., Milogiannakis, V., Jean, T., Esneau, C., Silva, M.R., Ison, T., Fichter, C., Lopez, J.A., Chandra, D., and Naing, Z. (2023). Emergence and Antibody Evasion of BQ, BA.2.75 and SARS-CoV-2 Recombinant Sub-Lineages in the Face of Maturing Antibody Breadth at the Population Level. EBioMedicine, 90.","DOI":"10.1016\/j.ebiom.2023.104545"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e143380","DOI":"10.1172\/JCI143380","article-title":"Recent Endemic Coronavirus Infection Is Associated with Less-Severe COVID-19","volume":"131","author":"Sagar","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2108395118","DOI":"10.1073\/pnas.2108395118","article-title":"How Immunity from and Interaction with Seasonal Coronaviruses Can Shape SARS-CoV-2 Epidemiology","volume":"118","author":"Waterlow","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/s41577-022-00809-x","article-title":"Nature Reviews Immunology The Impact of Pre-Existing Cross-Reactive Immunity on SARS-CoV-2 Infection and Vaccine Responses","volume":"23","author":"Murray","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8416","DOI":"10.1038\/s41598-023-35471-3","article-title":"Coronavirus Spike Protein-Specific Antibodies Indicate Frequent Infections and Reinfections in Infancy and among BNT162b2-Vaccinated Healthcare Workers","volume":"13","author":"Kolehmainen","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"105555","DOI":"10.1016\/j.antiviral.2023.105555","article-title":"Nirmatrelvir Exerts Distinct Antiviral Potency against Different Human Coronaviruses","volume":"211","author":"Li","year":"2023","journal-title":"Antivir. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1021\/acsmedchemlett.0c00521","article-title":"Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2","volume":"11","author":"Ghahremanpour","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2487","DOI":"10.1007\/s11224-020-01605-w","article-title":"Repurposing Metocurine as Main Protease Inhibitor to Develop Novel Antiviral Therapy for COVID-19","volume":"31","author":"Jain","year":"2020","journal-title":"Struct. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"236","DOI":"10.6026\/97320630016236","article-title":"Molecular Docking and Dynamics Simulation of FDA Approved Drugs with the Main Protease from 2019 Novel Coronavirus","volume":"16","author":"Odhar","year":"2020","journal-title":"Bioinformation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1007\/s13311-020-00992-6","article-title":"Anti-Prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation","volume":"18","author":"Bamia","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4125","DOI":"10.1021\/acs.jcim.1c00903","article-title":"Defending Antiviral Cationic Amphiphilic Drugs (CADs) That May Cause Drug-Induced Phospholipidosis Graphical Abstract HHS Public Access","volume":"61","author":"Lane","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s00018-022-04469-x","article-title":"The Double-Membrane Vesicle (DMV): A Virus-Induced Organelle Dedicated to the Replication of SARS-CoV-2 and Other Positive-Sense Single-Stranded RNA Viruses","volume":"79","author":"Roingeard","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1126\/science.abi4708","article-title":"Drug-Induced Phospholipidosis Confounds Drug Repurposing for SARS-CoV-2","volume":"373","author":"Tummino","year":"2021","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Caffrey, M., and Lavie, A. (2021). PH-Dependent Mechanisms of Influenza Infection Mediated by Hemagglutinin. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.777095"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1038\/s41579-019-0149-x","article-title":"Respiratory Syncytial Virus Entry and How to Block It","volume":"17","author":"Battles","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.phrs.2016.12.021","article-title":"Effect of Lysosomotropic Molecules on Cellular Homeostasis","volume":"117","author":"Kuzu","year":"2017","journal-title":"Pharmacol. Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"K\u00fchnl, A., Musiol, A., Heitzig, N., Johnson, D.E., Ehrhardt, C., Grewal, T., Gerke, V., Ludwig, S., and Rescher, U. (2018). Late Endosomal\/Lysosomal Cholesterol Accumulation Is a Host Cell-Protective Mechanism Inhibiting Endosomal Escape of Influenza A Virus. mBio, 9.","DOI":"10.1128\/mBio.01345-18"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Feng, Z., Xu, L., and Xie, Z. (2022). Receptors for Respiratory Syncytial Virus Infection and Host Factors Regulating the Life Cycle of Respiratory Syncytial Virus. Front. Cell Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.858629"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1089\/088318703322751327","article-title":"The Efficacy of Azelastine in the Prophylaxis of Acute Upper Respiratory Tract Infections","volume":"16","author":"Simon","year":"2003","journal-title":"Pediatr. Asthma Allergy Immunol."},{"key":"ref_41","unstructured":"(2023, October 24). ICTRP Search Portal. Available online: https:\/\/trialsearch.who.int\/Trial2.aspx?TrialID=DRKS00031059."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2300\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:28:43Z","timestamp":1760131723000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/15\/12\/2300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":41,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["v15122300"],"URL":"https:\/\/doi.org\/10.3390\/v15122300","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]}}}