Fig. 8: RAGE inhibitor azeliragon suppresses viral host inflammation responses and produces synergistic effects with molnupiravir when administered 2 h after infection.

a Graph showing the protein levels of S100A7 (left) and S100A8/A9 (right) in the vascular effluents of the alveolus chips at 48 hpi with HK/68 (H3N2) virus (MOI = 1) in the presence of 5% strain. Data represent mean ± SD; n = 3 biological chip replicates; unpaired two-tailed t-test. b Illustration of drug study on the human alveolus chip. c Graphs showing the levels of cytokines in the vascular effluents of alveolus chips that were uninfected (Ctrl), or infected with HK/68 (H3N2) (MOI = 1) in the presence or absence of 100 nM Azeliragon (Aze). Data are shown as mean ± SD; n = 3 biological chip replicates; one-way ANOVA with Dunnett’s multiple comparisons test. d Graph showing that azeliragon (100 nM) had no effect on viral load when administered 2 h after infection. Data are shown as mean ± SEM; n = 6 biological chip replicates; unpaired two-tailed t-test. e Plot showing the effect of molnupiravir at different concentrations on H3N2 viral load determined on human Alveolus Transwell. Data are shown as mean ± SD; n = 2 biological replicates. EC50 (half maximal effective concentration) was determined by a variable slope fitting with four parameters. f Graphs showing that azeliragon (100 nM) and molnupiravir (500 nM) drug combo synergistically reduce the levels of cytokines in the vascular effluents of alveolus chips infected with H3N2 virus. Data are shown as mean ± SEM; n = 3 biological chip replicates; one-way ANOVA with Dunnett’s multiple comparisons test. Source data are provided as a Source Data file.