Fig. 2: Host cell translation changes after infection with SARS-CoV-2.
From: Proteomics of SARS-CoV-2-infected host cells reveals therapy targets
a, Experimental scheme for translatome and proteome measurements. Caco-2 cells were infected with SARS-CoV-2 isolated from patients, incubated as indicated and analysed by quantitative translation and whole-cell proteomics. K8, lysine with 8 heavy isotopes; R10, arginine with 10 heavy isotopes; LC–MS/MS, Liquid chromatography–tandem mass spectrometry. b, Global translation rates, showed by distribution plots of mean log2-transformed fold changes of infected replicates to mock control for each time point and protein. The black line indicates the median and the dashed lines indicate 25% and 75% quantiles. Significance was tested by one-way ANOVA and two-sided post hoc Bonferroni test. ***P < 0.001 (10 h compared with 2 h, 4 × 10−26; 10 h compared with 6 h, 2.4 × 10−23; 10 h compared with 24 h, 2.3 × 10−28; n = 2,716 measured proteins averaged from 3 independent biological samples). c, Translation of viral proteins over time. Mean translation in arbitrary units (AU; normalized and corrected summed peptide spectrum matches were averaged) is plotted for control and infected samples. Shading indicates the s.d. (n = 3). d, Reactome pathway analysis of top 10% proteins following viral gene expression. Pathway results are shown with the number of proteins found in the dataset and computed FDRs for pathway enrichment. ER, endoplasmic reticulum. e, f, The antiviral assays show that the inhibition of viral replication is dependent on the concentrations of cycloheximide (e, n = 3) and emetine (f, n = 4). Each data point indicates biological replicates and the red line shows the dose–response curve fit. R2 and half-maximum inhibitory concentration (IC50) values were computed from the curve fit and the s.d. of the IC50 is indicated in parentheses. All n numbers represent independent biological samples if not stated otherwise.
