Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia
Abstract Antiviral strategies that target host systems needed for SARS‐CoV‐2 replication and pathogenesis may have therapeutic potential and help mitigate resistance development. Here, we evaluate nafamostat mesylate, a potent broad‐spectrum serine protease inhibitor that blocks host protease activa...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2022-02-01
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| Series: | Nano Select |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/nano.202100123 |
| _version_ | 1828890609509728256 |
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| author | Brian F. Niemeyer Caitlin M. Miller Carmen Ledesma‐Feliciano James H. Morrison Rocio Jimenez‐Valdes Clarissa Clifton Eric M. Poeschla Kambez H. Benam |
| author_facet | Brian F. Niemeyer Caitlin M. Miller Carmen Ledesma‐Feliciano James H. Morrison Rocio Jimenez‐Valdes Clarissa Clifton Eric M. Poeschla Kambez H. Benam |
| author_sort | Brian F. Niemeyer |
| collection | DOAJ |
| description | Abstract Antiviral strategies that target host systems needed for SARS‐CoV‐2 replication and pathogenesis may have therapeutic potential and help mitigate resistance development. Here, we evaluate nafamostat mesylate, a potent broad‐spectrum serine protease inhibitor that blocks host protease activation of the viral spike protein. SARS‐CoV‐2 is used to infect human polarized mucociliated primary bronchiolar epithelia reconstituted with cells derived from healthy donors, smokers and subjects with chronic obstructive pulmonary disease. Nafamostat markedly inhibits apical shedding of SARS‐CoV‐2 from all donors (log10 reduction). We also observe, for the first‐time, anti‐inflammatory effects of nafamostat on airway epithelia independent of its antiviral effects, suggesting a dual therapeutic advantage in the treatment of COVID‐19. Nafamostat also exhibits antiviral properties against the seasonal human coronaviruses 229E and NL6. These findings suggest therapeutic promise for nafamostat in treating SARS‐CoV‐2 and other human coronaviruses. |
| first_indexed | 2024-12-13T13:02:03Z |
| format | Article |
| id | doaj.art-8e8f02fb26a74936a5b8bcf03d8097e3 |
| institution | Directory Open Access Journal |
| issn | 2688-4011 |
| language | English |
| last_indexed | 2024-12-13T13:02:03Z |
| publishDate | 2022-02-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Nano Select |
| spelling | doaj.art-8e8f02fb26a74936a5b8bcf03d8097e32022-12-21T23:44:58ZengWiley-VCHNano Select2688-40112022-02-013243744910.1002/nano.202100123Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epitheliaBrian F. Niemeyer0Caitlin M. Miller1Carmen Ledesma‐Feliciano2James H. Morrison3Rocio Jimenez‐Valdes4Clarissa Clifton5Eric M. Poeschla6Kambez H. Benam7Division of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Infectious Diseases Department of Medicine Anschutz Medical Campus University of Colorado School of Medicine Aurora Colorado USADivision of Infectious Diseases Department of Medicine Anschutz Medical Campus University of Colorado School of Medicine Aurora Colorado USADivision of Infectious Diseases Department of Medicine Anschutz Medical Campus University of Colorado School of Medicine Aurora Colorado USADivision of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USADivision of Infectious Diseases Department of Medicine Anschutz Medical Campus University of Colorado School of Medicine Aurora Colorado USADivision of Pulmonary Allergy and Critical Care Medicine Department of Medicine University of Pittsburgh Pittsburgh Pennsylvania USAAbstract Antiviral strategies that target host systems needed for SARS‐CoV‐2 replication and pathogenesis may have therapeutic potential and help mitigate resistance development. Here, we evaluate nafamostat mesylate, a potent broad‐spectrum serine protease inhibitor that blocks host protease activation of the viral spike protein. SARS‐CoV‐2 is used to infect human polarized mucociliated primary bronchiolar epithelia reconstituted with cells derived from healthy donors, smokers and subjects with chronic obstructive pulmonary disease. Nafamostat markedly inhibits apical shedding of SARS‐CoV‐2 from all donors (log10 reduction). We also observe, for the first‐time, anti‐inflammatory effects of nafamostat on airway epithelia independent of its antiviral effects, suggesting a dual therapeutic advantage in the treatment of COVID‐19. Nafamostat also exhibits antiviral properties against the seasonal human coronaviruses 229E and NL6. These findings suggest therapeutic promise for nafamostat in treating SARS‐CoV‐2 and other human coronaviruses.https://doi.org/10.1002/nano.202100123SARS‐CoV‐2Nafamostatantiviralanti‐inflammatoryairway epithelium |
| spellingShingle | Brian F. Niemeyer Caitlin M. Miller Carmen Ledesma‐Feliciano James H. Morrison Rocio Jimenez‐Valdes Clarissa Clifton Eric M. Poeschla Kambez H. Benam Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia Nano Select SARS‐CoV‐2 Nafamostat antiviral anti‐inflammatory airway epithelium |
| title | Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| title_full | Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| title_fullStr | Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| title_full_unstemmed | Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| title_short | Broad antiviral and anti‐inflammatory efficacy of nafamostat against SARS‐CoV‐2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| title_sort | broad antiviral and anti inflammatory efficacy of nafamostat against sars cov 2 and seasonal coronaviruses in primary human bronchiolar epithelia |
| topic | SARS‐CoV‐2 Nafamostat antiviral anti‐inflammatory airway epithelium |
| url | https://doi.org/10.1002/nano.202100123 |
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