Article ; Online: NF-κB signalling as a pharmacological target in COVID-19: potential roles for IKKβ inhibitors.
Naunyn-Schmiedeberg's archives of pharmacology
2021 Volume 394, Issue 3, Page(s) 561–567
Abstract: Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the ... ...
Abstract | Coronavirus disease 2019 (COVID-19) has been characterized by lymphopenia as well as a proinflammatory cytokine storm, which are responsible for the poor prognosis and multiorgan defects. The transcription factor nuclear factor-κB (NF-κB) modulates the functions of the immune cells and alters the gene expression profile of different cytokines in response to various pathogenic stimuli, while many proinflammatory factors have been known to induce NF-κB signalling cascade. Besides, NF-κB has been known to potentiate the production of reactive oxygen species (ROS) leading to apoptosis in various tissues in many diseases and viral infections. Though the reports on the involvement of the NF-κB signalling pathway in COVID-19 are limited, the therapeutic benefits of NF-κB inhibitors including dexamethasone, a synthetic form of glucocorticoid, have increasingly been realized. Considering the fact, the abnormal activation of the NF-κB resulting from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might be associated with the pathogenic profile of immune cells, cytokine storm and multiorgan defects. Thus, the pharmacological inactivation of the NF-κB signalling pathway can strongly represent a potential therapeutic target to treat the symptomatology of COVID-19. This article signifies pharmacological blockade of the phosphorylation of inhibitor of nuclear factor kappa B kinase subunit beta (IKKβ), a key downstream effector of NF-κB signalling, for a therapeutic consideration to attenuate COVID-19. |
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MeSH term(s) | Animals ; COVID-19/drug therapy ; COVID-19/epidemiology ; COVID-19/metabolism ; Cytokine Release Syndrome/drug therapy ; Cytokine Release Syndrome/epidemiology ; Cytokine Release Syndrome/metabolism ; Drug Delivery Systems/trends ; Heterocyclic Compounds, 3-Ring/administration & dosage ; Humans ; I-kappa B Kinase/antagonists & inhibitors ; I-kappa B Kinase/metabolism ; Lymphopenia/drug therapy ; Lymphopenia/epidemiology ; Lymphopenia/metabolism ; NF-kappa B/antagonists & inhibitors ; NF-kappa B/metabolism ; Nitriles/administration & dosage ; Pyridines/administration & dosage ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Sulfones/administration & dosage |
Chemical Substances | 3-(4-methylphenylsulfonyl)-2-propenenitrile ; Heterocyclic Compounds, 3-Ring ; NF-kappa B ; Nitriles ; PS1145 ; Pyridines ; Sulfones ; I-kappa B Kinase (EC 2.7.11.10) ; IKBKB protein, human (EC 2.7.11.10) |
Language | English |
Publishing date | 2021-01-04 |
Publishing country | Germany |
Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Review |
ZDB-ID | 121471-8 |
ISSN | 1432-1912 ; 0028-1298 |
ISSN (online) | 1432-1912 |
ISSN | 0028-1298 |
DOI | 10.1007/s00210-020-02035-5 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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