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Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels?
The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However,...
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/PMC8269070/ https://www.ncbi.nlm.nih.gov/pubmed/34201797 http://dx.doi.org/10.3390/ijms22136764 |
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author | Kino, Tomoshige Burd, Irina Segars, James H. |
author_facet | Kino, Tomoshige Burd, Irina Segars, James H. |
author_sort | Kino, Tomoshige |
collection | PubMed |
description | The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them. |
format | Online Article Text |
id | pubmed-8269070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82690702021-07-10 Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? Kino, Tomoshige Burd, Irina Segars, James H. Int J Mol Sci Review The coronavirus disease 2019 (COVID-19) caused by infection of the severe respiratory syndrome coronavirus-2 (SARS-CoV-2) significantly impacted human society. Recently, the synthetic pure glucocorticoid dexamethasone was identified as an effective compound for treatment of severe COVID-19. However, glucocorticoids are generally harmful for infectious diseases, such as bacterial sepsis and severe influenza pneumonia, which can develop respiratory failure and systemic inflammation similar to COVID-19. This apparent inconsistency suggests the presence of pathologic mechanism(s) unique to COVID-19 that renders this steroid effective. We review plausible mechanisms and advance the hypothesis that SARS-CoV-2 infection is accompanied by infected cell-specific glucocorticoid insensitivity as reported for some other viruses. This alteration in local glucocorticoid actions interferes with undesired glucocorticoid to facilitate viral replication but does not affect desired anti-inflammatory properties in non-infected organs/tissues. We postulate that the virus coincidentally causes glucocorticoid insensitivity in the process of modulating host cell activities for promoting its replication in infected cells. We explore this tenet focusing on SARS-CoV-2-encoding proteins and potential molecular mechanisms supporting this hypothetical glucocorticoid insensitivity unique to COVID-19 but not characteristic of other life-threatening viral diseases, probably due to a difference in specific virally-encoded molecules and host cell activities modulated by them. MDPI 2021-06-23 /pmc/articles/PMC8269070/ /pubmed/34201797 http://dx.doi.org/10.3390/ijms22136764 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 | Review Kino, Tomoshige Burd, Irina Segars, James H. Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title | Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title_full | Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title_fullStr | Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title_full_unstemmed | Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title_short | Dexamethasone for Severe COVID-19: How Does It Work at Cellular and Molecular Levels? |
title_sort | dexamethasone for severe covid-19: how does it work at cellular and molecular levels? |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269070/ https://www.ncbi.nlm.nih.gov/pubmed/34201797 http://dx.doi.org/10.3390/ijms22136764 |
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