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

Authors :
Yaron TM
Heaton BE
Levy TM
Johnson JL
Jordan TX
Cohen BM
Kerelsky A
Lin TY
Liberatore KM
Bulaon DK
Van Nest SJ
Koundouros N
Kastenhuber ER
Mercadante MN
Shobana-Ganesh K
He L
Schwartz RE
Chen S
Weinstein H
Elemento O
Piskounova E
Nilsson-Payant BE
Lee G
Trimarco JD
Burke KN
Hamele CE
Chaparian RR
Harding AT
Tata A
Zhu X
Tata PR
Smith CM
Possemato AP
Tkachev SL
Hornbeck PV
Beausoleil SA
Anand SK
Aguet F
Getz G
Davidson AD
Heesom K
Kavanagh-Williamson M
Matthews DA
tenOever BR
Cantley LC
Blenis J
Heaton NS
Source :
Science signaling [Sci Signal] 2022 Oct 25; Vol. 15 (757), pp. eabm0808. Date of Electronic Publication: 2022 Oct 25.
Publication Year :
2022

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.

Details

Language :
English
ISSN :
1937-9145
Volume :
15
Issue :
757
Database :
MEDLINE
Journal :
Science signaling
Publication Type :
Academic Journal
Accession number :
36282911
Full Text :
https://doi.org/10.1126/scisignal.abm0808