Editors' ChoiceCORONAVIRUS

Growth factors and SARS-CoV-2

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Science Signaling  25 Aug 2020:
Vol. 13, Issue 646, eabe4450
DOI: 10.1126/scisignal.abe4450

Phosphoproteomics analysis reveals that blocking growth factor receptor signaling inhibits SARS-CoV-replication.

There is an urgent need to better understand the molecular mechanisms underlying infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that has caused the coronavirus disease 2019 (COVID-19) pandemic, so that effective therapies can be developed. Klann et al., performed phosphoproteomics analysis of a colonic epithelial cell line infected with SARS-CoV-2 in vitro to determine changes in the relative abundances (compared to those in mock-infected cells) of phosphorylated proteins 24 hours after infection. The authors first identified phosphorylation sites in six viral proteins expressed in the infected cells, many of which are targeted by kinases of CMGC family, which includes casein kinase II (CK2). Protein-protein coregulation analysis revealed three clusters of phosphorylated proteins that were affected by SARS-CoV-2 infection. One such cluster included proteins in signaling pathways activated by the growth factor receptors EGFR and PDGFR. The authors tested clinically approved anticancer drugs that inhibit the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways, both of which are downstream of growth factor receptors, and found five such drugs that inhibited SARS-CoV-2 replication in two different cell lines at clinically relevant concentrations. Together, these data provide a useful resource for the analysis of the signaling pathways affected by viral infection and indicate approved drugs that should be further investigated in other models of SARS-CoV-2 infection to determine whether they can be repurposed as antiviral agents.

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