The Global Phosphorylation Landscape of SARS-CoV-2 Infection

Mehdi Bouhaddou1, Danish Memon2, Bjoern Meyer3

  • 1QBI COVID-19 Research Group (QCRG), San Francisco, CA 94158, USA; Quantitative Biosciences Institute (QBI), University of California, San Francisco, San Francisco, CA 94158, USA; J. David Gladstone Institutes, San Francisco, CA 94158, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.

Cell
|July 10, 2020
PubMed

Insights

This study reveals how SARS-CoV-2 infection alters host cell phosphorylation, activating specific kinases and causing cell cycle arrest. Targeting these kinases with drugs shows potential for developing new severe acute respiratory syndrome coronavirus 2 therapies.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • The COVID-19 pandemic, caused by SARS-CoV-2, necessitates the development of effective antiviral treatments.
  • Understanding the molecular mechanisms of viral infection is crucial for identifying therapeutic targets.

Purpose of the Study:

  • To investigate the global phosphorylation changes in host and viral proteins during SARS-CoV-2 infection.
  • To identify potential drug targets and therapeutic compounds for COVID-19.

Main Methods:

  • Quantitative mass spectrometry-based phosphoproteomics was employed to analyze SARS-CoV-2 infected Vero E6 cells.
  • Global phosphorylation profiles were mapped to dysregulated kinases and pathways.

Main Results:

  • SARS-CoV-2 infection significantly altered host and viral protein phosphorylation.
  • Key findings include activation of casein kinase II (CK2) and p38 MAPK, cytokine production, and cell cycle arrest.
  • CK2-rich filopodial protrusions with budding viral particles were observed.

Conclusions:

  • Pharmacologic inhibition of specific kinases (p38, CK2, CDK, AXL, PIKFYVE) demonstrated antiviral efficacy against SARS-CoV-2.
  • These findings highlight potential therapeutic strategies for COVID-19 by targeting host-directed kinases.

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