Graphical abstract The coronavirus disease 19 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had turned out to be highly pathogenic and transmittable. Researchers throughout the globe are still struggling to understand this strain’s aggressiveness in search of putative therapies for its control. Crosstalk between oxidative stress and systemic inflammation seems to support the progression of the infection. Glycogen synthase kinase-3 (Gsk-3) is a conserved serine/threonine kinase that mainly participates in cell proliferation, development, stress, and inflammation in humans. Nucleocapsid protein of SARS-CoV-2 is an important structural protein responsible for viral replication and interferes with the host defence mechanism by the help of Gsk-3 protein. The viral infected cells show activated Gsk-3 protein that degrades the Nuclear factor erythroid 2-related factor (Nrf2) protein, resulting in excessive oxidative stress. Activated Gsk-3 also modulates CREB-DNA activity, phosphorylates NF-κB, and degrades β-catenin, thus provokes systemic inflammation. Interaction between these two pathophysiological events, oxidative stress, and inflammation enhance mucous secretion, coagulation cascade, and hypoxia, which ultimately leads to multiple organs failure, resulting in the death of the infected patient. The present review aims to highlight the pathogenic role of Gsk-3 in viral replication, initiation of oxidative stress, and inflammation during SARS-CoV-2 infection. The review also summarizes the potential Gsk-3 pathway modulators as putative therapeutic interventions in combating the COVID-19 pandemic.
【저자키워드】 COVID-19, SARS-CoV-2, SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2, oxidative stress, ACE2, angiotensin-converting enzyme 2, nucleocapsid protein, NF-κB, GSK-3, ARDS, acute respiratory distress syndrome, NTD, N-terminal domain, TNF, Tumor Necrosis Factor, MIP1α, Macrophage inflammatory protein 1α, NF-κB, nuclear factor-κB, GPX, glutathione peroxidase, NOX, NADPH oxidase, ROS, reactive oxygen species, COVID-19, coronavirus disease 19, PEDV, porcine epidemic diarrhea virus, ADP, adenosine diphosphate, ATP, adenosine triphosphate, vWF, von Willebrand factor, HCV, hepatitis C virus, IFN-γ, Interferon-gamma, AD, Alzheimer’s disease, aIIb/b3, Glycoprotein IIb/IIIa, ARE, Antioxidant response elements, ASC, Apoptosis-associated speck-like protein containing a CARD, BALF, Bronchoalveolar lavage, bZIP, Basic leucine zipper, CATs, Catalase, CBP, CREB binding protein, CREB, cAMP response element-binding protein, Cul3, Cullin 3, DAMP, Death associated molecular pattern, G-CSF, Granulocyte colony stimulating factor, GSH, Intracellular glutathione, Gsk-3, Glycogen synthase kinase-3, HDAC3, Histone deacetylase 3, HO-1, Heme Oxygenase-1, IKK, IkB Kinase, IL-6, Interleukin -6, IRAKs, Interleukin (IL)- 1R-associated kinase, IκB, Inhibitor of kappa B, Keap1, Kelch-like ECH associated protein 1, LiCl, Lithium chloride, MCP-1, Monocyte chemoattractant peptide, Myd88, Myeloid differentiation primary response 88, NAD(P)H, Nicotinamide adenine dinucleotide phosphate hydrogen, NLRP3, NOD-like receptors protein 3, NLRP3, Nucleotide-binding domain (NOD)-like receptor protein 3, N-protein, Nucleocapsid protein, Nrf2, Nuclear factor erythroid 2-related factor, O.−2, Superoxide anion, O2, Oxygen molecule, OxPLs, Oxidized phospholipids, PAMP, Pathogen associated molecular pattern, PAR, Protease-activated receptors, PD, Parkinson’s disease, PPRPattern, recognition receptor, PSGL, P-Selectin glycoprotein ligand-1, RIG-I, Retinoic acid-inducible gene I, sgmRNA, Sub genomic messenger RNA, SODs, Superoxide dismutase, TAK1, Transforming growth factor-β (TGF-β)-activated kinase 1, TF, Tissue factor, TIRAP, TIR-domain-containing adaptor protein, TLR-3, Toll like receptor-3, TNF-R, Tumor necrosis factor receptor, TNFα, Tumour necrosis factor-alpha, TRAF6, Tumour necrosis factor receptor associated factor 6, TRS, Transcription regulating sequence, XO, Xanthine oxidase, XOR, Xanthine oxidoreductase,