Fig. 2: 4-Octyl-itaconate (4-OI) and dimethyl fumarate (DMF) inhibit SARS-CoV2 replication.

(a–f) h TMPRSS2-Vero cells treated with 4-OI (48 h) and infected with SARS-CoV-2 (48 h). Viral replication by qPCR (a, b), TCID50-assay (c–e) or plaque assay (f). Are pooled data from four (a) and three (e) independent experiments in duplicates and triplicates. Data-points represent one biological sample. Data in (b), (c), and (d) are representative of two independent experiments. (f), supernatants from (e) analysed by plaque assay. Data are pooled from two independent experiments in duplicates. Data-points represent one biological sample. g TMPRSS2 cells with 4-OI and infected with SARS-CoV-2 for 48 h before LDH release-assay. Data pooled from two independent experiments in sextuplicates. h cells from (g) immunoblotted. Blot representative of two independent experiments. Calu3 cells with 4-OI and infected with SARS-CoV-2. Replication by qPCR (i) and TCID50 (j + k). Data pooled from two independent experiment in triplicates. l-m, NuLi cells treated with 4-OI and infected with SARS-CoV-2 for 48 h. Viral replication by TCID50. Data representative of two independent experiments in duplicates. n, HAE-culture graphic. o, HAE-cultures were treated with 4-OI overnight and infected with SARS-CoV-2. Viral replication by qPCR. p–r, Calu-3 and Vero hTMPRSS2 cells treated with DMF (150-200 μM) and infected with SARS-CoV-2. p is pooled data from three independent experiments in duplicates and triplicates. q is pooled data from two independent experiments in duplicates and triplicates. r is pooled data from two independent experiments in duplicates. siRNA treated Calu-3 cells infected with SARS-CoV2. Viral replication by qPCR (s), TCID50 (t), or immunoblotting (u). s is one representative of two independent experiments. t is pooled data from two independent experiments in duplicates. v, w, Vero cells treated with 4-OI at 125 µM and infected with SARS-CoV2 from Japan. Data in (u) is representative of two independent experiments, and (v) is pooled data from two independent experiments in duplicates and triplicates. Data in (w) is data from one experiment with two biological samples. Bars indicate mean ± s.e.m. Unless otherwise stated, statistical analyses by two-tailed Mann–Whitney (*p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001). P values: (a: p < 0.0001, e: p = 0.0002, f: 0.0286, g: p < 0.0001, i: p = 0.0022, k: p = 0.0022, m: p < 0.0001(two-tailed t test), o- p = 0.0268, p: p = 0.0002, q: p = 0.0079, r: p = 0.0286, t: p = 0.0286, v- p = 0.0079. Source data are provided as a Source Data file.