COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs

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, Efstathios Michalopoulos (Editor), Catherine Stavropoulos-Giokas (Editor), Panagiotis Mallis (Editor)

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.
Original languageEnglish
Article number13260
Number of pages23
JournalInternational Journal of Molecular Sciences
Issue number21
Early online date31 Oct 2022
Publication statusPublished - Nov 2022

Bibliographical note

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 (


  • 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)


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