Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses
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-O...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-06-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/17/7/890 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850071321606619136 |
|---|---|
| author | Elisa Feyles Tommaso Felicetti Irene Arduino Massimo Rittà Andrea Civra Luisa Muratori Stefania Raimondo David Lembo Giuseppe Manfroni Manuela Donalisio |
| author_facet | Elisa Feyles Tommaso Felicetti Irene Arduino Massimo Rittà Andrea Civra Luisa Muratori Stefania Raimondo David Lembo Giuseppe Manfroni Manuela Donalisio |
| author_sort | Elisa Feyles |
| collection | DOAJ |
| description | 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 EC<sub>50</sub> 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. |
| format | Article |
| id | doaj-art-3c4e68ec94744bc2baa4266df8d82d50 |
| institution | DOAJ |
| issn | 1999-4915 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-3c4e68ec94744bc2baa4266df8d82d502025-08-20T02:47:21ZengMDPI AGViruses1999-49152025-06-0117789010.3390/v17070890Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory VirusesElisa Feyles0Tommaso Felicetti1Irene Arduino2Massimo Rittà3Andrea Civra4Luisa Muratori5Stefania Raimondo6David Lembo7Giuseppe Manfroni8Manuela Donalisio9Laboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 1, 06123 Perugia, ItalyLaboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyLaboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyLaboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyDepartment of Clinical and Biological Sciences, Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyDepartment of Clinical and Biological Sciences, Neuroscience Institute Cavalieri Ottolenghi (NICO), University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyLaboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, Via del Liceo, 1, 06123 Perugia, ItalyLaboratory of Molecular Virology and Antiviral Research, Department of Clinical and Biological Sciences, University of Turin, Regione Gonzole 10, 10043 Orbassano, ItalyCell-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 EC<sub>50</sub> 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.https://www.mdpi.com/1999-4915/17/7/890antiviral agentsbroad-spectrum activityPyridobenzothiazolonesrespiratory tract infections |
| spellingShingle | Elisa Feyles Tommaso Felicetti Irene Arduino Massimo Rittà Andrea Civra Luisa Muratori Stefania Raimondo David Lembo Giuseppe Manfroni Manuela Donalisio Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses Viruses antiviral agents broad-spectrum activity Pyridobenzothiazolones respiratory tract infections |
| title | Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses |
| title_full | Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses |
| title_fullStr | Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses |
| title_full_unstemmed | Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses |
| title_short | Broad-Spectrum Antiviral Activity of Pyridobenzothiazolone Analogues Against Respiratory Viruses |
| title_sort | broad spectrum antiviral activity of pyridobenzothiazolone analogues against respiratory viruses |
| topic | antiviral agents broad-spectrum activity Pyridobenzothiazolones respiratory tract infections |
| url | https://www.mdpi.com/1999-4915/17/7/890 |
| work_keys_str_mv | AT elisafeyles broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT tommasofelicetti broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT irenearduino broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT massimoritta broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT andreacivra broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT luisamuratori broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT stefaniaraimondo broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT davidlembo broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT giuseppemanfroni broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses AT manueladonalisio broadspectrumantiviralactivityofpyridobenzothiazoloneanaloguesagainstrespiratoryviruses |