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; Catherine Stavropoulos-Giokas; Panagiotis Mallis

doi:10.3390/ijms232113260

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 journal › Review article › peer-review

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.

Original language	English
Article number	13260
Number of pages	23
Journal	International Journal of Molecular Sciences
Volume	23
Issue number	21
Early online date	31 Oct 2022
DOIs	https://doi.org/10.3390/ijms232113260
Publication status	Published - 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 (https://creativecommons.org/licenses/by/
4.0/).

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)

Access to Document

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ijms-23-13260-v2.pdf
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/).
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Cite this

Lee, J. H., Kanwar, B., Khattak, A., Balentine, J., Nguyen, N. H., Kast, R. E., Lee, C. J., Bourbeau, J., Altschuler, E. L., Sergi, C. M., Nguyen, T. N. M., Oh, S., Sohn, M.-G., Coleman, M., Michalopoulos, E. (Ed.), Stavropoulos-Giokas, C. (Ed.), & Mallis, P. (Ed.) (2022). COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs. International Journal of Molecular Sciences, 23(21), Article 13260. https://doi.org/10.3390/ijms232113260

@article{fe8729c6b7b046b99e9562f3be6f32b9,

title = "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.",

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)",

author = "Lee, {Jong Hoon} and Badar Kanwar and Asif Khattak and Jenny Balentine and Nguyen, {Ngoc Huy} and Kast, {Richard E.} and Lee, {Chul Joong} and Jean Bourbeau and Altschuler, {Eric L.} and Sergi, {Consolato M.} and Nguyen, {Tuan Ngoc Minh} and Sangsuk Oh and Mun-Gi Sohn and Michael Coleman and Efstathios Michalopoulos and Catherine Stavropoulos-Giokas and Panagiotis Mallis",

note = "Copyright: {\textcopyright} 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/). ",

year = "2022",

month = nov,

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Lee, JH, Kanwar, B, Khattak, A, Balentine, J, Nguyen, NH, Kast, RE, Lee, CJ, Bourbeau, J, Altschuler, EL, Sergi, CM, Nguyen, TNM, Oh, S, Sohn, M-G, Coleman, M, Michalopoulos, E (ed.), Stavropoulos-Giokas, C (ed.) & Mallis, P (ed.) 2022, 'COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs', International Journal of Molecular Sciences, vol. 23, no. 21, 13260. https://doi.org/10.3390/ijms232113260

TY - JOUR

T1 - COVID-19 Molecular Pathophysiology:

T2 - Acetylation of Repurposing Drugs

AU - Lee, Jong Hoon

AU - Kanwar, Badar

AU - Khattak, Asif

AU - Balentine, Jenny

AU - Nguyen, Ngoc Huy

AU - Kast, Richard E.

AU - Lee, Chul Joong

AU - Bourbeau, Jean

AU - Altschuler, Eric L.

AU - Sergi, Consolato M.

AU - Nguyen, Tuan Ngoc Minh

AU - Oh, Sangsuk

AU - Sohn, Mun-Gi

AU - Coleman, Michael

A2 - Michalopoulos, Efstathios

A2 - Stavropoulos-Giokas, Catherine

A2 - Mallis, Panagiotis

N1 - 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/).

PY - 2022/11

Y1 - 2022/11

N2 - 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.

AB - 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.

KW - ACE2 (angiotensin-converting enzyme 2)

KW - aspirin

KW - cGAS–STING (cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS)–stimulator of interferon genes (STING))

KW - dapsone

KW - dexamethasone

KW - immunologic engram

KW - inflammasome

KW - SAMHD1 (sterile alpha motif and histidine-aspartate domain-containing protein 1)

KW - SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)

KW - spike protein

KW - TLR4 (Toll-like receptor 4)

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U2 - 10.3390/ijms232113260

DO - 10.3390/ijms232113260

M3 - Review article

SN - 1661-6596

VL - 23

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

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M1 - 13260

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