{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:27:22Z","timestamp":1791433642471,"version":"4.3.3"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T00:00:00Z","timestamp":1750723200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Intesa Sanpaolo\u2014Fondo di Beneficenza","award":["B\/2022\/0185"],"award-info":[{"award-number":["B\/2022\/0185"]}]},{"name":"Intesa Sanpaolo\u2014Fondo di Beneficenza","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]},{"name":"EU funding within the MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases","award":["B\/2022\/0185"],"award-info":[{"award-number":["B\/2022\/0185"]}]},{"name":"EU funding within the MUR PNRR Extended Partnership Initiative on Emerging Infectious Diseases","award":["PE00000007"],"award-info":[{"award-number":["PE00000007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cell-based phenotypic screening of a privileged in-house library composed of pyridobenzothiazolone (PBTZ) analogues was conducted against representative viruses responsible for common respiratory tract infections in humans, i.e., respiratory syncytial virus (RSV), human coronavirus type OC43 (HCoV-OC43), and influenza virus type A (IFV-A). We identified a compound with broad-spectrum inhibitory activity against multiple strains of RSV, HCoV, and IFV, with EC50 values in the low micromolar range and cell-independent activity. Its antiviral activity and cytocompatibility were confirmed in a fully differentiated 3D model of the bronchial epithelium mimicking the in vivo setting. The hit compound enters cells and localizes homogeneously in the cytosol, inhibiting replicative phases in a virus-specific manner. Overall, the selected PBTZ represents a good starting point for further preclinical development as a broad-spectrum antiviral agent that could address the continuous threat of new emerging pathogens and the rising issue of antiviral resistance.<\/jats:p>","DOI":"10.3390\/v17070890","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T12:05:40Z","timestamp":1750766740000},"page":"890","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-6262-449X","authenticated-orcid":false,"given":"Elisa","family":"Feyles","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9369-8564","authenticated-orcid":false,"given":"Tommaso","family":"Felicetti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 1, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-670X","authenticated-orcid":false,"given":"Irene","family":"Arduino","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1612-8151","authenticated-orcid":false,"given":"Massimo","family":"Ritt\u00e0","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Civra","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4881-3313","authenticated-orcid":false,"given":"Luisa","family":"Muratori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8907-473X","authenticated-orcid":false,"given":"Stefania","family":"Raimondo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lembo","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0207-3927","authenticated-orcid":false,"given":"Giuseppe","family":"Manfroni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 1, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Donalisio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"ref_1","unstructured":"(2024, November 11). CDC About Respiratory Illnesses, Available online: https:\/\/www.cdc.gov\/respiratory-viruses\/about\/index.html."},{"key":"ref_2","unstructured":"Schmidt, T.M. (2019). Respiratory Viruses. Encyclopedia of Microbiology, Academic Press. [4th ed.]."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kumari, R., Sharma, S.D., Kumar, A., Ende, Z., Mishina, M., Wang, Y., Falls, Z., Samudrala, R., Pohl, J., and Knight, P.R. (2023). Antiviral Approaches against Influenza Virus. Clin. Microbiol. Rev., 36.","DOI":"10.1128\/cmr.00040-22"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1038\/s41579-023-00919-w","article-title":"Respiratory Syncytial Virus Infection and Novel Interventions","volume":"21","author":"Langedijk","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Outteridge, M., Nunn, C.M., Devine, K., Patel, B., and McLean, G.R. (2024). Antivirals for Broader Coverage against Human Coronaviruses. Viruses, 16.","DOI":"10.3390\/v16010156"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Geraghty, R.J., Aliota, M.T., and Bonnac, L.F. (2021). Broad-Spectrum Antiviral Strategies and Nucleoside Analogues. Viruses, 13.","DOI":"10.3390\/v13040667"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.antiviral.2019.03.004","article-title":"Broad Spectrum Anti-Flavivirus Pyridobenzothiazolones Leading to Less Infective Virions","volume":"167","author":"Cannalire","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"112992","DOI":"10.1016\/j.ejmech.2020.112992","article-title":"Sustainable, Three-Component, One-Pot Procedure to Obtain Active Anti-Flavivirus Agents","volume":"210","author":"Felicetti","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10530","DOI":"10.1002\/chem.201501271","article-title":"Asymmetric Isothiourea-Catalysed Formal [3+2] Cycloadditions of Ammonium Enolates with Oxaziridines","volume":"21","author":"Smith","year":"2015","journal-title":"Chemistry"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.antiviral.2016.09.007","article-title":"Targeting Flavivirus RNA Dependent RNA Polymerase through a Pyridobenzothiazole Inhibitor","volume":"134","author":"Tarantino","year":"2016","journal-title":"Antivir. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1016\/j.bmc.2011.11.061","article-title":"Pyridobenzothiazole Derivatives as New Chemotype Targeting the HCV NS5B Polymerase","volume":"20","author":"Manfroni","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.biomaterials.2016.01.055","article-title":"The AGMA1 Poly(Amidoamine) Inhibits the Infectivity of Herpes Simplex Virus in Cell Lines, in Human Cervicovaginal Histocultures, and in Vaginally Infected Mice","volume":"85","author":"Donalisio","year":"2016","journal-title":"Biomaterials"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"105897","DOI":"10.1016\/j.antiviral.2024.105897","article-title":"Polyoxometalate Exerts Broad-Spectrum Activity against Human Respiratory Viruses Hampering Viral Entry","volume":"226","author":"Arduino","year":"2024","journal-title":"Antivir. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.antiviral.2019.01.005","article-title":"Anti-Zika Virus Activity of Polyoxometalates","volume":"163","author":"Francese","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1021\/acsmedchemlett.9b00619","article-title":"Pyridobenzothiazolones Exert Potent Anti-Dengue Activity by Hampering Multiple Functions of NS5 Polymerase","volume":"11","author":"Cannalire","year":"2020","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Caracciolo, I., Mora-Cardenas, E., Aloise, C., Carletti, T., Segat, L., Burali, M.S., Chiarvesio, A., Totis, V., Av\u0161i\u010d\u2013\u017dupanc, T., and Mastrangelo, E. (2020). Comprehensive Response to Usutu Virus Following First Isolation in Blood Donors in the Friuli Venezia Giulia Region of Italy: Development of Recombinant NS1-Based Serology and Sensitivity to Antiviral Drugs. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008156"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Milan Bonotto, R., Bon\u00ec, F., Milani, M., Chaves-Sanjuan, A., Franze, S., Selmin, F., Felicetti, T., Bolognesi, M., Konstantinidou, S., and Poggianella, M. (2022). Virucidal Activity of the Pyridobenzothiazolone Derivative HeE1-17Y against Enveloped RNA Viruses. Viruses, 14.","DOI":"10.3390\/v14061157"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"105055","DOI":"10.1016\/j.antiviral.2021.105055","article-title":"Combined in Silico and in Vitro Approaches Identified the Antipsychotic Drug Lurasidone and the Antiviral Drug Elbasvir as SARS-CoV2 and HCoV-OC43 Inhibitors","volume":"189","author":"Milani","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Huang, B., Lin, B., Zheng, H., Zheng, B., Xue, X., and Liu, M. (2025). Discovery of Natural Products as Influenza Neuraminidase Inhibitors: In Silico Screening, in Vitro Validation, and Molecular Dynamic Simulation Studies. Mol. Divers.","DOI":"10.1007\/s11030-025-11115-8"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Florio Furno, M., Laiz\u00e9, V., Arduino, I., Pham, G.N., Spina, F., Mehiri, M., Lembo, D., Gavaia, P.J., and Varese, G.C. (2025). Bioprospecting Marine Fungi from the Plastisphere: Osteogenic and Antiviral Activities of Fungal Extracts. Mar. Drugs, 23.","DOI":"10.3390\/md23030115"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Rajan, A., Piedra, F.-A., Aideyan, L., McBride, T., Robertson, M., Johnson, H.L., Aloisio, G.M., Henke, D., Coarfa, C., and Stossi, F. (2022). Multiple Respiratory Syncytial Virus (RSV) Strains Infecting HEp-2 and A549 Cells Reveal Cell Line-Dependent Differences in Resistance to RSV Infection. J. Virol., 96.","DOI":"10.1128\/jvi.01904-21"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Felicetti, T., Gwee, C.P., Chan, K.W.K., Pepe, G., Milite, C., Campiglia, P., Watanabe, S., Mazlan, M.D.B.M., Sabatini, S., and Massari, S. (2025). New Pyridobenothiazolone Derivatives Display Nanomolar Pan-Serotype Anti-Dengue Virus Activity. ChemMedChem, 2500163.","DOI":"10.1002\/cmdc.202500163"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.antiviral.2018.06.007","article-title":"Antiviral Drug Screening by Assessing Epithelial Functions and Innate Immune Responses in Human 3D Airway Epithelium Model","volume":"156","author":"Boda","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1111\/bph.14221","article-title":"Late Therapeutic Intervention with a Respiratory Syncytial Virus L-Protein Polymerase Inhibitor, PC786, on Respiratory Syncytial Virus Infection in Human Airway Epithelium","volume":"175","author":"Brookes","year":"2018","journal-title":"Br. J. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"eaax9318","DOI":"10.1126\/sciadv.aax9318","article-title":"Modified Cyclodextrins as Broad-Spectrum Antivirals","volume":"6","author":"Jones","year":"2020","journal-title":"Sci. Adv."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/890\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:58:00Z","timestamp":1760032680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/7\/890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,24]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["v17070890"],"URL":"https:\/\/doi.org\/10.3390\/v17070890","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,24]]}}}