Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication.
dc.contributor.author | Yaron, Tomer M | |
dc.contributor.author | Heaton, Brook E | |
dc.contributor.author | Levy, Tyler M | |
dc.contributor.author | Johnson, Jared L | |
dc.contributor.author | Jordan, Tristan X | |
dc.contributor.author | Cohen, Benjamin M | |
dc.contributor.author | Kerelsky, Alexander | |
dc.contributor.author | Lin, Ting-Yu | |
dc.contributor.author | Liberatore, Katarina M | |
dc.contributor.author | Bulaon, Danielle K | |
dc.contributor.author | Van Nest, Samantha J | |
dc.contributor.author | Koundouros, Nikos | |
dc.contributor.author | Kastenhuber, Edward R | |
dc.contributor.author | Mercadante, Marisa N | |
dc.contributor.author | Shobana-Ganesh, Kripa | |
dc.contributor.author | He, Long | |
dc.contributor.author | Schwartz, Robert E | |
dc.contributor.author | Chen, Shuibing | |
dc.contributor.author | Weinstein, Harel | |
dc.contributor.author | Elemento, Olivier | |
dc.contributor.author | Piskounova, Elena | |
dc.contributor.author | Nilsson-Payant, Benjamin E | |
dc.contributor.author | Lee, Gina | |
dc.contributor.author | Trimarco, Joseph D | |
dc.contributor.author | Burke, Kaitlyn N | |
dc.contributor.author | Hamele, Cait E | |
dc.contributor.author | Chaparian, Ryan R | |
dc.contributor.author | Harding, Alfred T | |
dc.contributor.author | Tata, Aleksandra | |
dc.contributor.author | Zhu, Xinyu | |
dc.contributor.author | Tata, Purushothama Rao | |
dc.contributor.author | Smith, Clare M | |
dc.contributor.author | Possemato, Anthony P | |
dc.contributor.author | Tkachev, Sasha L | |
dc.contributor.author | Hornbeck, Peter V | |
dc.contributor.author | Beausoleil, Sean A | |
dc.contributor.author | Anand, Shankara K | |
dc.contributor.author | Aguet, François | |
dc.contributor.author | Getz, Gad | |
dc.contributor.author | Davidson, Andrew D | |
dc.contributor.author | Heesom, Kate | |
dc.contributor.author | Kavanagh-Williamson, Maia | |
dc.contributor.author | Matthews, David A | |
dc.contributor.author | tenOever, Benjamin R | |
dc.contributor.author | Cantley, Lewis C | |
dc.contributor.author | Blenis, John | |
dc.contributor.author | Heaton, Nicholas S | |
dc.date.accessioned | 2023-10-01T13:40:32Z | |
dc.date.available | 2023-10-01T13:40:32Z | |
dc.date.issued | 2022-10 | |
dc.date.updated | 2023-10-01T13:40:30Z | |
dc.description.abstract | 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. | |
dc.identifier.issn | 1945-0877 | |
dc.identifier.issn | 1937-9145 | |
dc.identifier.uri | ||
dc.language | eng | |
dc.publisher | American Association for the Advancement of Science (AAAS) | |
dc.relation.ispartof | Science signaling | |
dc.relation.isversionof | 10.1126/scisignal.abm0808 | |
dc.subject | Animals | |
dc.subject | Mammals | |
dc.subject | Humans | |
dc.subject | Nucleocapsid | |
dc.subject | Glycogen Synthase Kinase 3 | |
dc.subject | Threonine | |
dc.subject | Serine | |
dc.subject | Nucleocapsid Proteins | |
dc.subject | Virus Replication | |
dc.subject | Phosphorylation | |
dc.subject | COVID-19 | |
dc.subject | SARS-CoV-2 | |
dc.subject | Protein Serine-Threonine Kinases | |
dc.title | Host protein kinases required for SARS-CoV-2 nucleocapsid phosphorylation and viral replication. | |
dc.type | Journal article | |
duke.contributor.orcid | Trimarco, Joseph D|0000-0001-5463-7144 | |
duke.contributor.orcid | Tata, Aleksandra|0000-0003-3270-0485 | |
duke.contributor.orcid | Tata, Purushothama Rao|0000-0003-4837-0337 | |
duke.contributor.orcid | Smith, Clare M|0000-0003-2601-0955 | |
pubs.begin-page | eabm0808 | |
pubs.issue | 757 | |
pubs.organisational-group | Duke | |
pubs.organisational-group | School of Medicine | |
pubs.organisational-group | Student | |
pubs.organisational-group | Basic Science Departments | |
pubs.organisational-group | Clinical Science Departments | |
pubs.organisational-group | Institutes and Centers | |
pubs.organisational-group | Cell Biology | |
pubs.organisational-group | Molecular Genetics and Microbiology | |
pubs.organisational-group | Medicine | |
pubs.organisational-group | Medicine, Pulmonary, Allergy, and Critical Care Medicine | |
pubs.organisational-group | Duke Cancer Institute | |
pubs.organisational-group | Duke Human Vaccine Institute | |
pubs.organisational-group | Regeneration Next Initiative | |
pubs.publication-status | Published | |
pubs.volume | 15 |
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