COVID-19 Molecular Pathophysiology::Acetylation of Repurposing Drugs

Abstract

Abstract: 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-1production 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.

Publication DOI: https://doi.org/10.3390/ijms232113260
Divisions: College of Health & Life Sciences > Aston Pharmacy School
College of Health & Life Sciences
Additional Information: Copyright: © 2022 by the authors. 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/).
Uncontrolled Keywords: ACE2 (angiotensin-converting enzyme 2),aspirin,cGAS–STING (cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)–stimulator of interferon genes (STING)),dapsone,dexamethasone,immunologic engram,inflammasome,SAMHD1 (sterile alpha motif and histidine-aspartate domain-containing protein 1),SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2),spike protein,TLR4 (Toll-like receptor 4)
Publication ISSN: 1422-0067
Last Modified: 15 May 2024 16:45
Date Deposited: 16 Nov 2022 16:50
Full Text Link:
Related URLs: http://10.3390/ijms232113260 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Review article
Published Date: 2022-11
Published Online Date: 2022-10-31
Accepted Date: 2022-10-26
Authors: 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 (ORCID Profile 0000-0002-5510-6852)

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