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Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication

Tomer M Yaron1,2,3,4,5, Brook E Heaton6, Tyler M Levy7

  • 1Meyer Cancer Center, Weill Cornell Medicine, New York, NY 10021, USA.

Science Signaling
|October 25, 2022
PubMed

Insights

Researchers identified host protein kinases that phosphorylate the coronavirus N protein, a key step for viral replication. Inhibiting these kinases, like SRPK1/2, could offer broad therapeutic potential against various coronavirus diseases, including COVID-19.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Coronaviruses have caused lethal human diseases, necessitating treatments beyond vaccines.
  • Host factors are crucial for coronavirus replication and represent potential therapeutic targets.

Purpose of the Study:

  • To identify and characterize host protein kinases involved in the coronavirus replication cycle.
  • To investigate the role of specific kinase families (SRPK, GSK-3, CK1) in phosphorylating the viral N protein.

Main Methods:

  • Utilized knowledge of mammalian protein kinase substrate specificities.
  • Analyzed phosphorylation events on the viral N protein mediated by SRPK, GSK-3, and CK1 families.
  • Assessed the impact of SRPK1/2 inhibition on viral replication.

Main Results:

  • Deciphered the phosphorylation sequence of the viral N protein by SRPK, GSK-3, and CK1.
  • Demonstrated that SRPK1/2 initiates the N protein phosphorylation cascade.
  • Showed that loss or inhibition of SRPK1/2 significantly compromises coronavirus replication.

Conclusions:

  • Host protein kinases, particularly SRPK1/2, are essential for coronavirus replication.
  • Conserved N protein phosphorylation sites suggest broad therapeutic potential for kinase inhibitors against multiple coronaviruses.
  • Inhibitors targeting these host kinases may offer new treatments for COVID-19 and other coronavirus-induced diseases.

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