Journal: Cell

Article Title: The Global Phosphorylation Landscape of SARS-CoV-2 Infection

doi: 10.1016/j.cell.2020.06.034

Figure Lengend Snippet: Mapping Regulated Kinases to Kinase Inhibitors Identifies SARS-CoV-2 Therapies (A) Kinase inhibitors (left) mapped to kinases (right) whose activity was regulated by SARS-CoV-2 infection. Lines connecting them indicate known kinase targets for each drug/compound. (B) Vero E6 cells pre-treated with remdesivir at the indicated doses, followed by SARS-CoV-2 infection for 48 h. Percent viral titer compared with mock drug treatment (anti-NP antibody; red line, dots, and text) and cell viability (black) is depicted. Error bars represent SD. (C) As in (B). Vero E6 cells were treated with the CK2 inhibitor silmitasertib. Physical interactions between N protein and the CSNK2A2 and CSNK2B CK2 subunits were observed in a prior study ( Gordon et al., 2020 ). (D) Predicted increased kinase activity for the p38 signaling pathway and drugs/compounds targeting pathway members (ralimetinib, MAPK13-IN-1, and ARRY-797) and upstream drivers (gilteritinib). (E–G) As in (B). Vero E6 cells treated with the AXL inhibitor gilteritinib (E), the MAPK11/14 inhibitor ralimetinib (F), or the MAPK13 inhibitor MAPK13-IN-1 (G) prior to SARS-CoV-2 infection. (H) A549-ACE2 lung epithelial cells were treated with the MAPK14 inhibitor ARRY-797 prior to SARS-CoV-2 infection. (I) Small interfering RNA (siRNA) knockdown of p38 pathway genes in A549-ACE2 leads to a significant decrease in SARS-CoV-2 viral replication (red), as assessed by qRT-PCR in the absence of effects on cell viability (black). ACE2 and non-targeting siRNAs are included as positive and negative controls, respectively. (J and K) Vero E6 or A549-ACE2 cells were treated with PIKFYVE inhibitor apilimod (J) or the CDK inhibitor dinaciclib (K) prior to SARS-CoV-2 infection. See also Figure S6 .

Article Snippet: MAPK13-IN-1 , MedChemExpress , Cat#HY-18850; CAS#229002-10-2.

Techniques: Activity Assay, Infection, Small Interfering RNA, Quantitative RT-PCR

Journal: Cell

Article Title: The Global Phosphorylation Landscape of SARS-CoV-2 Infection

doi: 10.1016/j.cell.2020.06.034

Figure Lengend Snippet:

Article Snippet: MAPK13-IN-1 , MedChemExpress , Cat#HY-18850; CAS#229002-10-2.

Techniques: Recombinant, Produced, Protease Inhibitor, Sequencing, Modification, Electron Microscopy, MTT Assay, Cell Viability Assay, Infection, Functional Assay, Genomic Sequencing, Plasmid Preparation, Construct, Software, Microscopy, Laser-Scanning Microscopy, Real-time Polymerase Chain Reaction, Luminex, Transmission Assay, Imaging, Cytometry