RENACO - Repurposing of nafamostat mesylate for the treatment of COVID-19 - Subproject A

The novel, pandemic coronavirus (SARS-CoV-2) and the associated disease COVID-19 threaten public health and economies worldwide. In the light of a constantly rising death toll, drugs are urgently needed. The only way to meet this need is to repurpose drugs that have been approved for treatment of other diseases. We have recently shown that the cellular serine protease TMPRSS2 is essential for SARS-CoV-2 infection of lung cells and that a clinically proven TMPRSS2 inhibitor, camostat mesylate, blocks infection. Our recent results show that the FDA-approved serine protease inhibitor nafamostat mesylate, which is used in Japan for treatment of pancreatitis, has 50-fold higher antiviral activity as compared to camostat mesylate. The goal of the present study is to develop nafamostat mesylate for treatment of SARS-CoV-2 infection. For this, we will pursue three goals: First, as proof-of-concept, we will determine the antiviral activity of nafamostat mesylate in a non-human primate (NHP) model of SARS-CoV-2 infection. For this, the compound will be applied intravenously, the route of application used in pancreatitis patients. Second, we will analyze whether the compound can be nebulized and safely applied to the airways. For this, safety and pharmacokinetic studies of the inhaled drug will be conducted in rats and ex vivo lung tissue. Third, we will determine whether application of nafamostat mesylate to the upper respiratory tract of NHP as spray inhibits SARS-CoV-2 spread and could be used for prevention of COVID-19.