Fig 1: Concentration-dependent inhibition of TNF-R1–TNFα binding by compounds of the present study and corresponding selectivity plot. (A) Concentration–response curves obtained for the inhibition of this important TNF superfamily PPI in similar cell-free ELISA-type assay as used for the CoV-S–ACE2 PPIs to assess selectivity. Data and fit as before (Figure 3). As the IC50 values indicate, some of the DRI-C compounds showed more than 100-fold selectivity in inhibiting the CoV-S PPI vs the TNF PPI. (B) Selectivity plot comparing inhibitory activity (as quantified by log IC50) against the TNF-R1–TNF-α interaction with that against the desired PPI target (SARS-CoV-2-S-RBD–hACE2). Active and selective compounds are clustered in the lower right corner as highlighted by the trend-indicating arrows.