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Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection

SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications—including ibuprofen and other non-steroidal anti-inflamma...

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Autores principales: de Bruin, Natasja, Schneider, Ann-Kathrin, Reus, Philipp, Talmon, Sonja, Ciesek, Sandra, Bojkova, Denisa, Cinatl, Jindrich, Lodhi, Imran, Charlesworth, Bruce, Sinclair, Simon, Pennick, Graham, Laughey, William F., Gribbon, Philip, Kannt, Aimo, Schiffmann, Susanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835123/
https://www.ncbi.nlm.nih.gov/pubmed/35162972
http://dx.doi.org/10.3390/ijms23031049
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author de Bruin, Natasja
Schneider, Ann-Kathrin
Reus, Philipp
Talmon, Sonja
Ciesek, Sandra
Bojkova, Denisa
Cinatl, Jindrich
Lodhi, Imran
Charlesworth, Bruce
Sinclair, Simon
Pennick, Graham
Laughey, William F.
Gribbon, Philip
Kannt, Aimo
Schiffmann, Susanne
author_facet de Bruin, Natasja
Schneider, Ann-Kathrin
Reus, Philipp
Talmon, Sonja
Ciesek, Sandra
Bojkova, Denisa
Cinatl, Jindrich
Lodhi, Imran
Charlesworth, Bruce
Sinclair, Simon
Pennick, Graham
Laughey, William F.
Gribbon, Philip
Kannt, Aimo
Schiffmann, Susanne
author_sort de Bruin, Natasja
collection PubMed
description SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications—including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)—have the potential to upregulate ACE2, thereby possibly facilitating viral entry and increasing the severity of COVID-19. We investigated the influence of the NSAIDS with a range of cyclooxygenase (COX)1 and COX2 selectivity (ibuprofen, flurbiprofen, etoricoxib) and paracetamol on the level of ACE2 mRNA/protein expression and activity as well as their influence on SARS-CoV-2 infection levels in a Caco-2 cell model. We also analysed the ACE2 mRNA/protein levels and activity in lung, heart and aorta in ibuprofen treated mice. The drugs had no effect on ACE2 mRNA/protein expression and activity in the Caco-2 cell model. There was no up-regulation of ACE2 mRNA/protein expression and activity in lung, heart and aorta tissue in ibuprofen-treated mice in comparison to untreated mice. Viral load was significantly reduced by both flurbiprofen and ibuprofen at high concentrations. Ibuprofen, flurbiprofen, etoricoxib and paracetamol demonstrated no effects on ACE2 expression or activity in vitro or in vivo. Higher concentrations of ibuprofen and flurbiprofen reduced SARS-CoV-2 replication in vitro.
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spelling pubmed-88351232022-02-12 Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection de Bruin, Natasja Schneider, Ann-Kathrin Reus, Philipp Talmon, Sonja Ciesek, Sandra Bojkova, Denisa Cinatl, Jindrich Lodhi, Imran Charlesworth, Bruce Sinclair, Simon Pennick, Graham Laughey, William F. Gribbon, Philip Kannt, Aimo Schiffmann, Susanne Int J Mol Sci Article SARS-CoV-2 uses the human cell surface protein angiotensin converting enzyme 2 (ACE2) as the receptor by which it gains access into lung and other tissue. Early in the pandemic, there was speculation that a number of commonly used medications—including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)—have the potential to upregulate ACE2, thereby possibly facilitating viral entry and increasing the severity of COVID-19. We investigated the influence of the NSAIDS with a range of cyclooxygenase (COX)1 and COX2 selectivity (ibuprofen, flurbiprofen, etoricoxib) and paracetamol on the level of ACE2 mRNA/protein expression and activity as well as their influence on SARS-CoV-2 infection levels in a Caco-2 cell model. We also analysed the ACE2 mRNA/protein levels and activity in lung, heart and aorta in ibuprofen treated mice. The drugs had no effect on ACE2 mRNA/protein expression and activity in the Caco-2 cell model. There was no up-regulation of ACE2 mRNA/protein expression and activity in lung, heart and aorta tissue in ibuprofen-treated mice in comparison to untreated mice. Viral load was significantly reduced by both flurbiprofen and ibuprofen at high concentrations. Ibuprofen, flurbiprofen, etoricoxib and paracetamol demonstrated no effects on ACE2 expression or activity in vitro or in vivo. Higher concentrations of ibuprofen and flurbiprofen reduced SARS-CoV-2 replication in vitro. MDPI 2022-01-19 /pmc/articles/PMC8835123/ /pubmed/35162972 http://dx.doi.org/10.3390/ijms23031049 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
de Bruin, Natasja
Schneider, Ann-Kathrin
Reus, Philipp
Talmon, Sonja
Ciesek, Sandra
Bojkova, Denisa
Cinatl, Jindrich
Lodhi, Imran
Charlesworth, Bruce
Sinclair, Simon
Pennick, Graham
Laughey, William F.
Gribbon, Philip
Kannt, Aimo
Schiffmann, Susanne
Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title_full Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title_fullStr Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title_full_unstemmed Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title_short Ibuprofen, Flurbiprofen, Etoricoxib or Paracetamol Do Not Influence ACE2 Expression and Activity In Vitro or in Mice and Do Not Exacerbate In-Vitro SARS-CoV-2 Infection
title_sort ibuprofen, flurbiprofen, etoricoxib or paracetamol do not influence ace2 expression and activity in vitro or in mice and do not exacerbate in-vitro sars-cov-2 infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8835123/
https://www.ncbi.nlm.nih.gov/pubmed/35162972
http://dx.doi.org/10.3390/ijms23031049
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