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A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug
The term cytokine storm refers to an uncontrolled overproduction of soluble inflammatory markers known as cytokines and chemokines. Autoimmune destruction of the lungs triggered by the release of these inflammatory markers often induces acute respiratory distress syndrome (ARDS). ARDS is an emergenc...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698520/ https://www.ncbi.nlm.nih.gov/pubmed/34943719 http://dx.doi.org/10.3390/antibiotics10121507 |
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author | Morgan, Paul Arnold, Shareen J. Hsiao, Nai-Wan Shu, Chih-Wen |
author_facet | Morgan, Paul Arnold, Shareen J. Hsiao, Nai-Wan Shu, Chih-Wen |
author_sort | Morgan, Paul |
collection | PubMed |
description | The term cytokine storm refers to an uncontrolled overproduction of soluble inflammatory markers known as cytokines and chemokines. Autoimmune destruction of the lungs triggered by the release of these inflammatory markers often induces acute respiratory distress syndrome (ARDS). ARDS is an emergency condition with a high mortality rate in COVID-19 patients. Dexamethasone is the first repurposed corticosteroid with life-saving efficacy in patients with severe SARS-CoV-2 infection. Dexamethasone has traditionally been known to suppress the production of inflammatory markers at the transcriptional level, but its role as a direct therapeutic to neutralize cytokines, chemokines, their receptors, and functionally critical SARS-CoV-2 proteins has not yet been explored. Herein, we demonstrated that dexamethasone binds with high affinity to interlukin-1 (IL-1), IL-6, IL-8, IL-12, IL-21, INF2, TGFβ-1, INF-γ, CXCL8, some of the receptors, IL-1R, IL-21R, IFNGR, INFAR, IL-6αR-gp130, ST2 and the SARS-CoV-2 protein NSP macro X, and 3CLpro, forming stable drug–protein complexes. Our work implied that dexamethasone has the potential to directly neutralize inflammatory markers, further supporting its life-saving potential in patients with severe manifestations of COVID-19. |
format | Online Article Text |
id | pubmed-8698520 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86985202021-12-24 A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug Morgan, Paul Arnold, Shareen J. Hsiao, Nai-Wan Shu, Chih-Wen Antibiotics (Basel) Article The term cytokine storm refers to an uncontrolled overproduction of soluble inflammatory markers known as cytokines and chemokines. Autoimmune destruction of the lungs triggered by the release of these inflammatory markers often induces acute respiratory distress syndrome (ARDS). ARDS is an emergency condition with a high mortality rate in COVID-19 patients. Dexamethasone is the first repurposed corticosteroid with life-saving efficacy in patients with severe SARS-CoV-2 infection. Dexamethasone has traditionally been known to suppress the production of inflammatory markers at the transcriptional level, but its role as a direct therapeutic to neutralize cytokines, chemokines, their receptors, and functionally critical SARS-CoV-2 proteins has not yet been explored. Herein, we demonstrated that dexamethasone binds with high affinity to interlukin-1 (IL-1), IL-6, IL-8, IL-12, IL-21, INF2, TGFβ-1, INF-γ, CXCL8, some of the receptors, IL-1R, IL-21R, IFNGR, INFAR, IL-6αR-gp130, ST2 and the SARS-CoV-2 protein NSP macro X, and 3CLpro, forming stable drug–protein complexes. Our work implied that dexamethasone has the potential to directly neutralize inflammatory markers, further supporting its life-saving potential in patients with severe manifestations of COVID-19. MDPI 2021-12-08 /pmc/articles/PMC8698520/ /pubmed/34943719 http://dx.doi.org/10.3390/antibiotics10121507 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Morgan, Paul Arnold, Shareen J. Hsiao, Nai-Wan Shu, Chih-Wen A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title | A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title_full | A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title_fullStr | A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title_full_unstemmed | A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title_short | A Closer Look at Dexamethasone and the SARS-CoV-2-Induced Cytokine Storm: In Silico Insights of the First Life-Saving COVID-19 Drug |
title_sort | closer look at dexamethasone and the sars-cov-2-induced cytokine storm: in silico insights of the first life-saving covid-19 drug |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8698520/ https://www.ncbi.nlm.nih.gov/pubmed/34943719 http://dx.doi.org/10.3390/antibiotics10121507 |
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