Fig. 3: Validation of EIDD-1931 drug interactions affecting %Inhibition in the propagated, original SARS-CoV-2 strain.
a, b Surface plots of EIDD-1931 interactions with remdesivir (RDV) and baricitinib (BRT) in the validation interaction space, clinically actionable interaction space (black, solid line border) and the interaction space from the IDentif.AI-x analysis (black, dotted line border). The latter two are also shown as two-dimensional maps. All experiments were performed with N = 3 to 4 replicates, which were independently included in the surface construction. Black, round markers indicate an average %Inhibition of the replicates for each treatment. Adjusted R2 (Adj R2) indicates goodness of the fit for each interaction surface. c, d Dose-response curves (D-R curves) of EIDD-1931 in monotherapy and in a combination with RDV and BRT at two concentration ratios: the ratio tested in the IDentif.AI-x experimental set (OACD ratio) and the ratio dictated by the Cmax values of the drugs (Cmax ratio). Half maximal absolute effective concentration (EC50) was derived from the D-R curves, which is the concentration that resulted in 50% Inhibition. The vertical line marks the 10% Cmax of EIDD-1931. Please note that the EIDD-1931-only EC50 values (Green) were provided in both subfigures c and d to enable direct comparisons with both combinations (EIDD-1931/RDV and EIDD-1931/BRT). The entire assay was completed in one experiment, realizing all data points in a single global study, and enabling comprehensive derivation of combinations and direct comparisons between monotherapies and combinations. Error bars represent propagated standard deviation (s.d.; N = 3 to 4 replicates). Of note, this propagated s.d. did not arise from the replicates’ spread, but from plate-to-plate variation (s.d. of the controls). No statistically significant difference between the D-R curves was detected with sum of square F test.
