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COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AM...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656873/ https://www.ncbi.nlm.nih.gov/pubmed/36362045 http://dx.doi.org/10.3390/ijms232113260 |
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author | Lee, Jong Hoon Kanwar, Badar Khattak, Asif Balentine, Jenny Nguyen, Ngoc Huy Kast, Richard E. Lee, Chul Joong Bourbeau, Jean Altschuler, Eric L. Sergi, Consolato M. Nguyen, Tuan Ngoc Minh Oh, Sangsuk Sohn, Mun-Gi Coleman, Michael |
author_facet | Lee, Jong Hoon Kanwar, Badar Khattak, Asif Balentine, Jenny Nguyen, Ngoc Huy Kast, Richard E. Lee, Chul Joong Bourbeau, Jean Altschuler, Eric L. Sergi, Consolato M. Nguyen, Tuan Ngoc Minh Oh, Sangsuk Sohn, Mun-Gi Coleman, Michael |
author_sort | Lee, Jong Hoon |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions. |
format | Online Article Text |
id | pubmed-9656873 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96568732022-11-15 COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs Lee, Jong Hoon Kanwar, Badar Khattak, Asif Balentine, Jenny Nguyen, Ngoc Huy Kast, Richard E. Lee, Chul Joong Bourbeau, Jean Altschuler, Eric L. Sergi, Consolato M. Nguyen, Tuan Ngoc Minh Oh, Sangsuk Sohn, Mun-Gi Coleman, Michael Int J Mol Sci Review Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces immune-mediated type 1 interferon (IFN-1) production, the pathophysiology of which involves sterile alpha motif and histidine-aspartate domain-containing protein 1 (SAMHD1) tetramerization and the cytosolic DNA sensor cyclic-GMP-AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway. As a result, type I interferonopathies are exacerbated. Aspirin inhibits cGAS-mediated signaling through cGAS acetylation. Acetylation contributes to cGAS activity control and activates IFN-1 production and nuclear factor-κB (NF-κB) signaling via STING. Aspirin and dapsone inhibit the activation of both IFN-1 and NF-κB by targeting cGAS. We define these as anticatalytic mechanisms. It is necessary to alleviate the pathologic course and take the lag time of the odds of achieving viral clearance by day 7 to coordinate innate or adaptive immune cell reactions. MDPI 2022-10-31 /pmc/articles/PMC9656873/ /pubmed/36362045 http://dx.doi.org/10.3390/ijms232113260 Text en © 2022 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 Lee, Jong Hoon Kanwar, Badar Khattak, Asif Balentine, Jenny Nguyen, Ngoc Huy Kast, Richard E. Lee, Chul Joong Bourbeau, Jean Altschuler, Eric L. Sergi, Consolato M. Nguyen, Tuan Ngoc Minh Oh, Sangsuk Sohn, Mun-Gi Coleman, Michael COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title | COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title_full | COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title_fullStr | COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title_full_unstemmed | COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title_short | COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs |
title_sort | covid-19 molecular pathophysiology: acetylation of repurposing drugs |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9656873/ https://www.ncbi.nlm.nih.gov/pubmed/36362045 http://dx.doi.org/10.3390/ijms232113260 |
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