The clinically approved small molecule protease inhibitors camostat and nafamostat have been shown to inhibit TMPRSS2 activity in vitro and have undergone drug repurposing efforts for TMPRSS2-targeted SARS-CoV-2 antiviral therapy . Camostat and nafamostat share the same electrophilic 4-guanidino benzoate core that specifically binds to Subsite 1 (S1) of trypsin-like serine proteases and then reacts with the catalytic serine residue to form an inactive enzyme adduct, shown in Fig. for TMPRSS2. Camostat and nafamostat were developed to treat pancreatitis and to be used as an anticoagulant , respectively.