Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters
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
Affiliations
Megan Neary
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Joanne Sharp
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Eduardo Gallardo-Toledo
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Joanne Herriott
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Edyta Kijak
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Chloe Bramwell
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Helen Cox
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Lee Tatham
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Helen Box
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Paul Curley
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Usman Arshad
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Rajith K. R. Rajoli
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Henry Pertinez
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Anthony Valentijn
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
Kevin Dhaliwal
Translational Healthcare Technologies Group, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh EH10 5HF, UK
Frank Mc Caughan
Victor Phillip Dahdaleh Heart and Lung Research Institute, Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Papworth Road, Cambridge CB2 1BN, UK
James Hobson
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L3 5TR, UK
Steve Rannard
Centre of Excellence in Long-Acting Therapeutics (CELT), University of Liverpool, Liverpool L3 5TR, UK
Anja Kipar
Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5TR, UK
James P. Stewart
Department of Infection Biology & Microbiomes, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L3 5TR, UK
Andrew Owen
Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L3 5TR, UK
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 (p = 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 (p = 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.
