Fig. 3: SARS-CoV-2 infection profiling reveals cellular pathways that are essential for replication.

a, Patterns of protein levels across all samples. The proteins that were significantly up- or downregulated (two-sided, unpaired Student’s t-test with equal variance assumed, P < 0.05, n = 3) in at least one infected sample compared with the corresponding control are shown. Data were standardized using Z-scoring before row-wise clustering and plotting. TCA, tricarboxylic acid. b, Reactome pathway analysis of the protein network created from cluster II, which includes host cell proteins that are increased after SARS-CoV-2 infection (a; Supplementary Table 4). Pathway results are shown with the number of proteins found in the dataset and computed FDR for pathway enrichment. c, Functional interaction network of proteins found annotated to carbon metabolism in the Reactome pathway analysis. Lines indicate functional interactions. d, e, The antiviral assays show that the inhibition of viral replication is dependent on the concentrations of pladienolide B (d, n = 3) and 2-deoxy-d-glucose (e, n = 3). Each data point indicates a biological replicate and the red line shows the dose–response curve fit. R² and IC₅₀ values were computed from the curve fit and the s.d. of IC₅₀ is indicated in parentheses. C_max, maximum plasma concentration; E7107, the indicated C_max was obtained for the E7107, a derivative of pladienolide B. All n numbers represent independent biological samples.