The '2602 compound showed moderate TMPRSS2 selectivity over related proteases thrombin, TMPRSS13, but inhibited trypsin and TMPRSS3 at similar levels to 6-amidino-2-naphthol (Extended Data Fig. ). To improve the potency and TMPRSS2 selectivity of future '2222 and '2602 derivative compounds, more TMPRSS2-specific amino acids within the substrate binding cleft could be targeted. As noted in our previous work , the TMPRSS2 Lys342 residue situated within S2 is relatively distinct amongst TTSPs and could potentially be targeted for H-bonding or salt bridges with a ligand.