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Evaluation of Nafamostat as Chemoprophylaxis for SARS-CoV-2 Infection in Hamsters.

Published version

Published version
Peer-reviewed

Repository DOI


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Authors

Gallardo-Toledo, Eduardo 
Herriott, Joanne 
Kijak, Edyta 

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 (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.

Description

Peer reviewed: True


Funder: Unitaid

Keywords

SARS-CoV-2, chemoprophylaxis, nafamostat, Animals, Cricetinae, COVID-19, SARS-CoV-2, RNA, Viral, Chemoprevention, Mesocricetus

Journal Title

Viruses

Conference Name

Journal ISSN

1999-4915
1999-4915

Volume Title

15

Publisher

MDPI AG
Sponsorship
MRC (via Imperial College London) (MR/W005611/1)