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


Multiple coronaviruses have emerged independently in the past 20 years that cause lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated or who experience breakthrough infections. Understanding the common host factors necessary for the life cycles of coronaviruses may reveal conserved therapeutic targets. Here, we used the known substrate specificities of mammalian protein kinases to deconvolute the sequence of phosphorylation events mediated by three host protein kinase families (SRPK, GSK-3, and CK1) that coordinately phosphorylate a cluster of serine and threonine residues in the viral N protein, which is required for viral replication. We also showed that loss or inhibition of SRPK1/2, which we propose initiates the N protein phosphorylation cascade, compromised the viral replication cycle. Because these phosphorylation sites are highly conserved across coronaviruses, inhibitors of these protein kinases not only may have therapeutic potential against COVID-19 but also may be broadly useful against coronavirus-mediated diseases.





Published Version (Please cite this version)


Publication Info

Yaron, Tomer M, Brook E Heaton, Tyler M Levy, Jared L Johnson, Tristan X Jordan, Benjamin M Cohen, Alexander Kerelsky, Ting-Yu Lin, et al. (2022). Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication. Science signaling, 15(757). p. eabm0808. 10.1126/scisignal.abm0808 Retrieved from

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Brook Heaton

Assistant Research Professor of Molecular Genetics and Microbiology

Aleksandra Tata

Assistant Research Professor of Cell Biology

Purushothama Rao Tata

Associate Professor of Cell Biology

Lung regeneration
Lung stem cells
Cell plasticity
Organoid models
Lung Fibrosis
Single Cell Biology


Clare Smith

Assistant Professor of Molecular Genetics and Microbiology

The Smith Lab are interested in host genetic diversity, bacterial variation, and how these host-pathogen genetic interactions drive tuberculosis disease states.

Systems Genetics of Tuberculosis
: We leverage host diversity in mice and macrophages from wild-derived mouse strains and diverse mouse panels, including the Collaborative Cross and BXD mammalian resources. In parallel, we define the bacterial genetic requirements for growth and adaptation across these diverse host environments through cutting-edge mycobacterial genetic approaches. These combined host and bacterial genome-wide approaches allows the interrogation of each host-pathogen interaction underlying tuberculosis disease, drug treatments and vaccine interventions. 


Nicholas Scott Heaton

Associate Professor of Molecular Genetics and Microbiology

Our research group is primarily interested in the study of respiratory RNA viruses.  We have published work on viruses of the families: orthomyxoviridae, paramyxoviridae, and coronaviridae.  The research in our laboratory is predominantly focused understanding the mechanisms of viral pathogenesis with the ultimate goal of developing new therapies that can be used to combat both current and future viral diseases.

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