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10.1016/j.molcel.2020.08.006

http://scihub22266oqcxt.onion/10.1016/j.molcel.2020.08.006
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32877642!7418786!32877642
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suck abstract from ncbi


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pmid32877642      Mol+Cell 2020 ; 80 (1): 164-174.e4
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  • Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication #MMPMID32877642
  • Klann K; Bojkova D; Tascher G; Ciesek S; Munch C; Cinatl J
  • Mol Cell 2020[Oct]; 80 (1): 164-174.e4 PMID32877642show ga
  • SARS-CoV-2 infections are rapidly spreading around the globe. The rapid development of therapies is of major importance. However, our lack of understanding of the molecular processes and host cell signaling events underlying SARS-CoV-2 infection hinders therapy development. We use a SARS-CoV-2 infection system in permissible human cells to study signaling changes by phosphoproteomics. We identify viral protein phosphorylation and define phosphorylation-driven host cell signaling changes upon infection. Growth factor receptor (GFR) signaling and downstream pathways are activated. Drug-protein network analyses revealed GFR signaling as key pathways targetable by approved drugs. The inhibition of GFR downstream signaling by five compounds prevents SARS-CoV-2 replication in cells, assessed by cytopathic effect, viral dsRNA production, and viral RNA release into the supernatant. This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as a central pathway essential for SARS-CoV-2 replication. It provides novel strategies for COVID-19 treatment.
  • |Adrenal Cortex Hormones/therapeutic use[MESH]
  • |Angiotensin-Converting Enzyme Inhibitors/therapeutic use[MESH]
  • |Antibodies, Neutralizing/therapeutic use[MESH]
  • |Antiviral Agents/*therapeutic use[MESH]
  • |Betacoronavirus/*drug effects/immunology/pathogenicity[MESH]
  • |Caco-2 Cells[MESH]
  • |Gene Expression Regulation[MESH]
  • |Host-Pathogen Interactions/drug effects/genetics[MESH]
  • |Humans[MESH]
  • |Mitogen-Activated Protein Kinases/antagonists & inhibitors/*genetics/metabolism[MESH]
  • |Phosphatidylinositol 3-Kinase/*genetics/metabolism[MESH]
  • |Phosphoproteins/antagonists & inhibitors/genetics/metabolism[MESH]
  • |Phosphorylation[MESH]
  • |Receptors, Growth Factor/antagonists & inhibitors/*genetics/metabolism[MESH]
  • |SARS-CoV-2[MESH]
  • |Signal Transduction[MESH]
  • |Viral Proteins/antagonists & inhibitors/*genetics/metabolism[MESH]


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