Growth Factor Receptor Signaling Inhibition Prevents SARS-CoV-2 Replication.
Mol Cell
; 80(1): 164-174.e4, 2020 10 01.
Article
in English
| MEDLINE | ID: covidwho-709380
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Viral Proteins
/
Receptors, Growth Factor
/
Mitogen-Activated Protein Kinases
/
Phosphatidylinositol 3-Kinase
/
Betacoronavirus
Limits:
Humans
Language:
English
Journal:
Mol Cell
Journal subject:
Molecular Biology
Year:
2020
Document Type:
Article
Affiliation country:
J.molcel.2020.08.006
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