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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,...

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Detalles Bibliográficos
Autores principales: Kino, Tomoshige, Burd, Irina, Segars, James H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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