COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Nov 11

PMID 36362045

Authors

Jong Hoon Lee

Badar Kanwar

Asif Khattak

Jenny Balentine

Ngoc Huy Nguyen

Richard E Kast

Chul Joong Lee

Jean Bourbeau

Eric L Altschuler

Consolato M Sergi

Tuan Ngoc Minh Nguyen

Sangsuk Oh

Mun-Gi Sohn

Michael Coleman

Affiliations

Soon will be listed here.

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-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.

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