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
| Autor: | Natasja de Bruin, Ann-Kathrin Schneider, Philipp Reus, Sonja Talmon, Sandra Ciesek, Denisa Bojkova, Jindrich Cinatl, Imran Lodhi, Bruce Charlesworth, Simon Sinclair, Graham Pennick, William F. Laughey, Philip Gribbon, Aimo Kannt, Susanne Schiffmann |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2022 |
| Předmět: |
Male
NSAIDs QH301-705.5 ACE2 mRNA expression Gene Expression Regulation Enzymologic Catalysis Inorganic Chemistry Etoricoxib Mice Animals Humans Biology (General) Physical and Theoretical Chemistry QD1-999 Molecular Biology Spectroscopy Acetaminophen ibuprofen ACE2 activity SARS-CoV-2 SARS-CoV-2 infection organic chemicals Anti-Inflammatory Agents Non-Steroidal Organic Chemistry COVID-19 General Medicine Virus Internalization Computer Science Applications Enzyme Activation Mice Inbred C57BL Chemistry Flurbiprofen ACE protein expression Disease Progression Angiotensin-Converting Enzyme 2 Caco-2 Cells hormones hormone substitutes and hormone antagonists |
| Zdroj: | International Journal of Molecular Sciences, Vol 23, Iss 1049, p 1049 (2022) International Journal of Molecular Sciences; Volume 23; Issue 3; Pages: 1049 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23031049 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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