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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...

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Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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
Descripción
Sumario: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.