2. Academic Validation
  3. Evidence for investigating GSK-3 inhibitors as potential therapeutics for severe COVID-19

Evidence for investigating GSK-3 inhibitors as potential therapeutics for severe COVID-19

  • Biochem Biophys Res Commun. 2022 May 21;605:171-176. doi: 10.1016/j.bbrc.2022.03.035.
Davoud Ghazanfari 1,  Maria Cecilia Courreges 2,  Lydia Belinski 1,  Stephen C Bergmeier 3,  Kelly D McCall 4,  Douglas J Goetz 5
Affiliations

Affiliations

  • 1 Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH, 45701, United States.
  • 2 Department of Specialty Medicine, Ohio University, Athens, OH, 45701, United States.
  • 3 Biomedical Engineering Program, Ohio University, Athens, OH, 45701, United States; Department of Chemistry and Biochemistry, Ohio University, Athens, OH, 45701, United States.
  • 4 Department of Specialty Medicine, Ohio University, Athens, OH, 45701, United States; Biomedical Engineering Program, Ohio University, Athens, OH, 45701, United States; The Diabetes Institute, Ohio University, Athens, OH, 45701, United States.
  • 5 Department of Chemical and Biomolecular Engineering, Ohio University, Athens, OH, 45701, United States; Biomedical Engineering Program, Ohio University, Athens, OH, 45701, United States. Electronic address: goetzd@ohio.edu.
PMID: 35367865 DOI: 10.1016/j.bbrc.2022.03.035
Abstract

A key component of severe COVID-19 is a "cytokine storm" i.e., the excessive expression of unneeded cytokines. Previous studies suggest that SARS-CoV-2 Proteins can induce macrophages to secrete pro-inflammatory cytokines; a process that may involve Toll-like receptors (TLRs). Glycogen synthase kinase-3 (GSK-3) has been implicated in TLR signal transduction and a selective GSK-3 Inhibitor, termed COB-187, dramatically attenuates cytokine expression induced by the TLR ligand lipopolysaccharide (LPS). In the present study, we provide evidence that the SARS-CoV-2 spike protein (S) and the S2 subunit (S2) induce production of CXCL10 (a chemokine elevated in severe COVID-19) by a human macrophage cell line. Further, we report that two clinically relevant GSK-3 inhibitors and COB-187 attenuate S and S2 protein-induced CXCL10 production. Combined, our observations provide impetus for investigating GSK-3 inhibitors as potential therapeutics for severe COVID-19.

Keywords

COVID-19; CXCL10; Cytokine storm; Glycogen synthase kinase-3; Spike protein.

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