Neary, Megan 
ORCID: 0000-0002-4960-2139, Sharp, Joanne, Gallardo-Toledo, Eduardo, Herriott, Joanne, Kijak, Edyta, Bramwell, Chloe, Cox, Helen, Tatham, Lee ORCID: 0000-0001-9448-8876, Box, Helen, Curley, Paul ORCID: 0000-0003-4596-2708 et al (show 11 more authors)
(2023)
Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.
VIRUSES-BASEL, 15 (8).
1744-.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | chemoprophylaxis, nafamostat, SARS-CoV-2 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Science and Engineering > School of Physical Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 29 Sep 2023 09:24 |
| Last Modified: | 29 Sep 2023 09:24 |
| DOI: | 10.3390/v15081744 |
| Open Access URL: | https://doi.org/10.3390/v15081744 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173200 |
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