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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
Summary
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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