GSK-3 Inhibition as a Therapeutic Approach Against SARs CoV2: Dual Benefit of Inhibiting Viral Replication While Potentiating the Immune Response

Frontiers in Immunology
Christopher E Rudd

Abstract

The SARS-CoV2 (COVID-19) pandemic and uncertainties in developing a vaccine have created an urgent need for new therapeutic approaches. A key question is whether it is possible to make rational predictions of new therapies based on the presently available scientific and medical information. In this regard, I have noticed an omission in the present analysis in the literature related to the exploitation of glycogen synthase kinase 3 (GSK-3) as a therapeutic approach. This is based on two key observations, that GSK-3 inhibitors can simultaneously block SARs viral replication, while boosting CD8+ adaptive T-cell and innate natural killer (NK) responses. Firstly, it is already clear that GSK-3 phosphorylation of SARs CoV1 N protein on key serine residues is needed for viral replication such that small molecule inhibitors (SMIs) of GSK-3 can inhibit viral replication. In comparing protein sequences, I show here that the key sites in the N protein of SARs CoV1 N for replication are conserved in SARs CoV2. This strongly suggests that GSK-3 SMIs will also inhibit SARs Cov2 replication. Secondly, we and others have previously documented that GSK-3 SMIs markedly enhance CD8+ cytolytic T-cell (CTL) and NK cell anti-viral effector functions...Continue Reading

References

Jul 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·C E RuddS F Schlossman
Oct 31, 2003·Proceedings of the National Academy of Sciences of the United States of America·Haitao YangZihe Rao
Feb 21, 2006·FEMS Immunology and Medical Microbiology·Tetsuya MizutaniShigeru Morikawa
Feb 16, 2010·Nature Reviews. Immunology·Margarida Saraiva, Anne O'Garra
Jun 21, 2011·Nature Immunology·Vanja Lazarevic, Laurie H Glimcher
Nov 9, 2011·Frontiers in Molecular Neuroscience·Hagit Eldar-Finkelman, Ana Martinez
Sep 1, 2012·Journal of Alzheimer's Disease : JAD·Teodoro del SerTeresa León
Apr 29, 2016·American Journal of Physiology. Renal Physiology·Rujun GongLance Dworkin
Dec 17, 2016·Current Opinion in Immunology·Viola C Lam, Lewis L Lanier
Feb 27, 2017·Current Topics in Developmental Biology·Prital Patel, James R Woodgett
Apr 20, 2017·Immunity·Janna Krueger, Christopher E Rudd
Aug 10, 2017·Cancer Research·Frank CichockiJeffrey S Miller
Apr 8, 2020·Immunity·Fatima Amanat, Florian Krammer
Dec 1, 2007·International Journal of Mass Spectrometry·Liang LinSiqi Liu
May 1, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jyoti Madhusoodanan
May 22, 2020·International Journal of Bipolar Disorders·Andrea MurruUNKNOWN International Group for The Study of Lithium Treated Patients (IGSLi)

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Citations

Jun 4, 2021·Journal of Medicinal Chemistry·Thanigaimalai Pillaiyar, Stefan Laufer
Oct 2, 2021·Proceedings of the National Academy of Sciences of the United States of America·Xiaolei LiuPeter S Klein

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