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

Yaron, Tomer M

Heaton, Brook E

Levy, Tyler M

Johnson, Jared L

Jordan, Tristan X

Cohen, Benjamin M

Kerelsky, Alexander

Lin, Ting-Yu

Liberatore, Katarina M

Bulaon, Danielle K

Van Nest, Samantha J

Koundouros, Nikos

Kastenhuber, Edward R

Mercadante, Marisa N

Shobana-Ganesh, Kripa

He, Long

Schwartz, Robert E

Chen, Shuibing

Weinstein, Harel

Elemento, Olivier

Piskounova, Elena

Nilsson-Payant, Benjamin E

Lee, Gina

Trimarco, Joseph D

Burke, Kaitlyn N

Hamele, Cait E

Chaparian, Ryan R

Harding, Alfred T

Tata, Aleksandra

Zhu, Xinyu

Tata, Purushothama Rao

Smith, Clare M

Possemato, Anthony P

Tkachev, Sasha L

Hornbeck, Peter V

Beausoleil, Sean A

Anand, Shankara K

Aguet, François

Getz, Gad

Davidson, Andrew D

Heesom, Kate

Kavanagh-Williamson, Maia

Matthews, David A

tenOever, Benjamin R

Cantley, Lewis C

Blenis, John

Heaton, Nicholas S

2023-10-01T13:40:32Z

2023-10-01T13:40:32Z

2022-10

2023-10-01T13:40:30Z

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.

1945-0877

1937-9145

https://hdl.handle.net/10161/29042

eng

American Association for the Advancement of Science (AAAS)

Science signaling

10.1126/scisignal.abm0808

Animals

Mammals

Humans

Nucleocapsid

Glycogen Synthase Kinase 3

Threonine

Serine

Nucleocapsid Proteins

Virus Replication

Phosphorylation

COVID-19

SARS-CoV-2

Protein Serine-Threonine Kinases

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

Journal article

Trimarco, Joseph D|0000-0001-5463-7144

Tata, Aleksandra|0000-0003-3270-0485

Tata, Purushothama Rao|0000-0003-4837-0337

Smith, Clare M|0000-0003-2601-0955

eabm0808

757

Duke

School of Medicine

Student

Basic Science Departments

Clinical Science Departments

Institutes and Centers

Cell Biology

Molecular Genetics and Microbiology

Medicine

Medicine, Pulmonary, Allergy, and Critical Care Medicine

Duke Cancer Institute

Duke Human Vaccine Institute

Regeneration Next Initiative

Published

15