ArticleMolecular biomedicine2022
Inhibition of glycogen synthase kinase-3-beta (GSK3β) blocks nucleocapsid phosphorylation and SARS-CoV-2 replication.
Article in Molecular biomedicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Direct interaction between human DDX1 and SARS-CoV-2 nucleocapsid protein is regulated by phosphorylation.The Journal of biological chemistry · 2026Article
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- The dual role of glycogen synthase kinase-3 beta (GSK3β) in neurodegenerative pathologies: interplay between autophagy and disease progression.Frontiers in pharmacology · 2025Review
- SARS-CoV-2 evolution balances conflicting roles of N protein phosphorylation.PLoS pathogens · 2024Article
- ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis.Journal of virology · 2024Article
- Glycogen synthase kinase 3 inhibition controlsiScience · 2024Article
- ISGylation of the SARS-CoV-2 N protein by HERC5 impedes N oligomerization and thereby viral RNA synthesis.bioRxiv : the preprint server for biology · 2024Article
- Synthesis and Evaluation of 5-(Heteroarylmethylene)hydantoins as Glycogen Synthase Kinase-3β Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Modular characterization of SARS-CoV-2 nucleocapsid protein domain functions in nucleocapsid-like assembly.Molecular biomedicine · 2023Article
- Melatonin: Regulation of Viral Phase Separation and Epitranscriptomics in Post-Acute Sequelae of COVID-19.International journal of molecular sciences · 2022Review
- Lithium salts as a treatment for COVID-19: Pre-clinical outcomes.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
GSK3β has been proposed to have an essential role in Coronaviridae infections. Screening of a targeted library of GSK3β inhibitors against both SARS-CoV-2 and HCoV-229E to identify broad-spectrum anti-Coronaviridae inhibitors resulted in the identification of a high proportion of active compounds with low toxicity to host cells. A selected lead compound, T-1686568, showed low micromolar, dose-dependent activity against SARS-CoV-2 and HCoV-229E. T-1686568 showed efficacy in viral-infected cultured cells and primary 2D organoids. T-1686568 also inhibited SARS-CoV-2 variants of concern Delta and Omicron. Importantly, while inhibition by T-1686568 resulted in the overall reduction of viral load and protein translation, GSK3β inhibition resulted in cellular accumulation of the nucleocapsid protein relative to the spike protein. Following identification of potential phosphorylation sites of Coronaviridae nucleocapsid, protein kinase substrate profiling assays combined with Western blotting analysis of nine host kinases showed that the SARS-CoV-2 nucleocapsid could be phosphorylated by GSK3β and PKCa. GSK3β phosphorylated SARS-CoV-2 nucleocapsid on the S180/S184, S190/S194 and T198 phospho-sites, following previous priming in the adjacent S188, T198 and S206, respectively. Such inhibition presents a compelling target for broad-spectrum anti-Coronaviridae compound development, and underlies the mechanism of action of GSK3β host-directed therapy against this class of obligate intracellular pathogens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.