Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters
The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprop...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-08-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/8/1744 |
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| author | Megan Neary Joanne Sharp Eduardo Gallardo-Toledo Joanne Herriott Edyta Kijak Chloe Bramwell Helen Cox Lee Tatham Helen Box Paul Curley Usman Arshad Rajith K. R. Rajoli Henry Pertinez Anthony Valentijn Kevin Dhaliwal Frank Mc Caughan James Hobson Steve Rannard Anja Kipar James P. Stewart Andrew Owen |
| author_facet | Megan Neary Joanne Sharp Eduardo Gallardo-Toledo Joanne Herriott Edyta Kijak Chloe Bramwell Helen Cox Lee Tatham Helen Box Paul Curley Usman Arshad Rajith K. R. Rajoli Henry Pertinez Anthony Valentijn Kevin Dhaliwal Frank Mc Caughan James Hobson Steve Rannard Anja Kipar James P. Stewart Andrew Owen |
| author_sort | Megan Neary |
| collection | DOAJ |
| description | The successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (<i>p</i> = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (<i>p</i> = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection. |
| first_indexed | 2024-03-10T23:30:27Z |
| format | Article |
| id | doaj.art-24438ca2f944447a88cab0056c860073 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T23:30:27Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-24438ca2f944447a88cab0056c8600732023-11-19T03:21:11ZengMDPI AGViruses1999-49152023-08-01158174410.3390/v15081744Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in HamstersMegan Neary0Joanne Sharp1Eduardo Gallardo-Toledo2Joanne Herriott3Edyta Kijak4Chloe Bramwell5Helen Cox6Lee Tatham7Helen Box8Paul Curley9Usman Arshad10Rajith K. R. Rajoli11Henry Pertinez12Anthony Valentijn13Kevin Dhaliwal14Frank Mc Caughan15James Hobson16Steve Rannard17Anja Kipar18James P. Stewart19Andrew Owen20Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKTranslational Healthcare Technologies Group, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH10 5HF, UKVictor Phillip Dahdaleh Heart and Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Papworth Road, Cambridge CB2 1BN, UKCentre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L3 5TR, UKCentre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L3 5TR, UKDepartment of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5TR, UKDepartment of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5TR, UKDepartment of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UKThe successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention that is implementable alongside vaccination programmes. Nafamostat is a serine protease inhibitor that inhibits SARS-CoV-2 entry in vitro, but it has not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and has an extremely short plasma half-life. This study sought to determine whether intranasal dosing of nafamostat at 5 mg/kg twice daily was able to prevent the airborne transmission of SARS-CoV-2 from infected to uninfected Syrian Golden hamsters. SARS-CoV-2 RNA was detectable in the throat swabs of the water-treated control group 4 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, throat swabs from the intranasal nafamostat-treated hamsters remained SARS-CoV-2 RNA negative for the full 4 days of cohabitation. Significantly lower SARS-CoV-2 RNA concentrations were seen in the nasal turbinates of the nafamostat-treated group compared to the control (<i>p</i> = 0.001). A plaque assay quantified a significantly lower concentration of infectious SARS-CoV-2 in the lungs of the nafamostat-treated group compared to the control (<i>p</i> = 0.035). When taken collectively with the pathological changes observed in the lungs and nasal mucosa, these data are strongly supportive of the utility of intranasally delivered nafamostat for the prevention of SARS-CoV-2 infection.https://www.mdpi.com/1999-4915/15/8/1744SARS-CoV-2nafamostatchemoprophylaxis |
| spellingShingle | Megan Neary Joanne Sharp Eduardo Gallardo-Toledo Joanne Herriott Edyta Kijak Chloe Bramwell Helen Cox Lee Tatham Helen Box Paul Curley Usman Arshad Rajith K. R. Rajoli Henry Pertinez Anthony Valentijn Kevin Dhaliwal Frank Mc Caughan James Hobson Steve Rannard Anja Kipar James P. Stewart Andrew Owen Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters Viruses SARS-CoV-2 nafamostat chemoprophylaxis |
| title | Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters |
| title_full | Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters |
| title_fullStr | Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters |
| title_full_unstemmed | Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters |
| title_short | Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters |
| title_sort | evaluation of nafamostat as chemoprophylaxis for sars cov 2 infection in hamsters |
| topic | SARS-CoV-2 nafamostat chemoprophylaxis |
| url | https://www.mdpi.com/1999-4915/15/8/1744 |
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