Fig. 4: TBK1 inhibition limits SARS-CoV-2-driven hyper-inflammation.

a Daily weights of K18-hACE2 mice after intranasal infection (day 0) with 10³ PFU SARS-CoV-2. Idronoxil [IDX]/MRT67307 [MRT]/H151/vehicle injections were performed on days 3, 4, and 5, with mice culled on day 5 post-infection (n = 6 animals were examined per group in one experiment). Veh is vehicle, SARS is SARS-CoV-2 infected, and Sham is non-infected. b Bronchoalveolar lavage fluid [BALF] cell subsets were enumerated following Modified Giemsa staining to distinguish cell populations (n = 6 animals were examined per group in one experiment, however one outlier in the SARS + Vehicle group was removed in the Neutrophils analyses). c Histology of fixed lung lobes with associated inflammatory scores (n = 6 animals were examined per group in one experiment). d Alveolar thickness in the primary airways determined by histology (n = 6 animals were examined per group in one experiment). e Cytokine quantification in lung homogenates (n = 6 animals were examined per group in one experiment, however one outlier in each but the SARS + Vehicle group was removed in the CXCL1 analyses after ROUT outlier analysis). f mRNA transcript levels in lung homogenates. Expression of indicated genes is shown relative to Hprt (n = 6 animals were examined per group in one experiment). a–f Data are mean ± s.e.m. a Two-way or (b–f) one-way ANOVA with uncorrected Fisher’s LSD (with single pooled variance) multiple comparisons are shown. Exact p values are shown for all comparisons except for (a) where the comparisons for days 0, 1, 2 and 3 are provided in Source Data File, and where “ns” is non-significant (p > 0.05). Source data and detailed statistical analyses are provided as a Source Data file.