Abstract
Successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection
prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine
protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for
chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and
while camostat is orally available, both drugs have extremely short plasma half-lives. This study
sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne
transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral
RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days
after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated
hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over
the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-
treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility
of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are
underway to confirm absence of pulmonary infection and pathological changes.
prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine
protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for
chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and
while camostat is orally available, both drugs have extremely short plasma half-lives. This study
sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne
transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral
RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days
after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated
hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over
the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-
treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility
of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are
underway to confirm absence of pulmonary infection and pathological changes.
| Original language | English |
|---|---|
| Publisher | bioRxiv |
| Number of pages | 18 |
| DOIs | |
| Publication status | Published - 8 Jul 2021 |