After the experimental TMPRSS2 crystal structure was published , we also performed a virtual screen of the experimentally determined TMPRSS2 binding pocket against the ZINC-22 library . This screen contained over 200 million monocations. The pocket was optimized using the same parameters as the TMPRSS2 homology model. In this screen, a set of 59 compounds were prioritized for testing. Six compounds in the selected pool of noncovalent compounds shared a N-[4-(aminomethyl)-3fluorophenyl]acetamide substitution which we defined as Scaffold 7 and two of six Scaffold 7 compounds, '2222 and '2602, demonstrated measurable TMPRSS2 inhibition with IC50 valules of 23 µM and 59 µM, respectively (Fig. ; Extended Data Fig. ).