The Global Phosphorylation Landscape of SARS-CoV-2 Infection
By Mehdi Bouhaddou, Danish Memon, Bjoern Meyer, K. White, V. Rezelj, Miguel Correa Marrero, B. Polacco, James E. Melnyk, Svenja Ulferts, Robyn M. Kaake and 68 more. Cell, 2020
946 citations recorded by the source corpus.
The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.
Subfields: Cell Biology, Immunology, Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/c1b9a83dc83b538f281bdaf6ad0265fd9615cc70
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In Cell Biology
Citations in the corpus
- The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions (2020, background): “30 Known inhibitors of many other host cell factors that interact with viral proteins 30,31,33 or host cell signaling networks altered by viral infection 34 represent candidates for repurposed therapeutics against SARS-CoV-2.”
- Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis (2020, critical): “While the two use cases at the end of the paper describe potential biological applications, I find the resulting findings rather vague, and I guess biologists would not learn too many new things from it.”
- The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19 (2020, neutral): “The latter groups of autoantibody targets are interesting in the context of SARS-CoV-2 infection, because a recently published analysis of global phosphorylation patterns in SARS-CoV-2 infected cells reported strong upregulation of casein-kinase 2 activity, and potent antiviral activity of a drug, s”