SARS-CoV-2 phosphoproteomics - ACE2-A549 and Vero

Multiple coronavirus have emerged independently in the past 20 years and caused lethal human diseases. Although vaccine development targeting these viruses has been accelerated substantially, there remain patients requiring treatment who cannot be vaccinated. Understanding the common host factors necessary for the life cycle 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 phosphorylate a cluster of serine and threonine residues on the viral N-protein in a highly coordinated way. We showed that these kinases were critical for the viral replication cycle, suggesting that inhibitors of one or more of these protein kinases could be useful for treating patients with COVID-19 infections. These phosphorylation sites are highly conserved across coronaviruses, indicating that inhibitors of these protein kinases might be broadly effective in treating multiple viral diseases.