Fig. 2: Plitidepsin decreases the early translation of SARS-CoV-2 proteins required for the late synthesis of structural viral proteins. | Nature Communications

Fig. 2: Plitidepsin decreases the early translation of SARS-CoV-2 proteins required for the late synthesis of structural viral proteins.

From: Targeting eEF1A reprograms translation and uncovers broad-spectrum antivirals against cap or m6A protein synthesis routes

Fig. 2

A Protein detection and significance obtained with a two-sided linear model adjusted with Benjamini–Hochberg false discovery rate (FDR) in SARS-CoV-2 exposed versus non-infected cells ± 50 nM plitidepsin. Volcano plots of 6533 proteins consistently detected in all assayed samples comparing Log 10 of adjusted P-values and Log 2 fold change (FC). Dotted lines indicate P = 0.05. P Significantly downregulated cellular proteins are shown in yellow dots, upregulated in blue. Gray dots represent proteins with no variation. Viral proteins are shown in red. Proteins are listed in Supplementary Data 1. B Differences in abundance (Log 2 intensity distribution) of the indicated viral proteins in cells exposed to SARS-CoV-2 (orange) and not exposed (green) ± 0.5, 5 and 50 nM of plitidepsin. Interquartile range (IQR), and first, second and third quartiles (Q) are shown. Whiskers extend 1.5 times the IQR from Q1 and Q3. Data from A and B derive from n rep = 3 analyzed for each condition tested. C Percentage of Vero E6 cells positive for dsRNA detected by FACS. Cells ± 50 nM plitidepsin were inoculated with D614G for 48 h (P = 0.0002). Data show mean and S.D. from n exp = 3 and n rep = 8. D Confocal microscopy of dsRNA (green) of Vero E6 cells treated as in C. Nuclei were labeled with DAPI (blue). Scale bar 50 µm. E Cell-associated nucleocapsid and spike content detected by ELISA in Vero E6 cells infected with D614G ± 50 nM of plitidepsin followed over time (P = 0.0022). Mean and S.D. for each timepoint of n exp = 3 and n rep = 6. C and E statistical differences were assayed with a two-sided Mann–Whitney U test 48 h post-infection. F Confocal microscopy of nucleocapsid (green) and spike (red) staining of Vero E6 cells infected with D614G ± 50 nM of plitidepsin (Scale bar 50 µm). Highlighted inset is magnified (Scale bars 25 µm). Nuclei were labeled with DAPI (blue). Source Data file provides source data.

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