{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T02:19:13Z","timestamp":1773886753536,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"LOEWE Centre for Translational Biodiversity Genomics","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["CARS"],"award-info":[{"award-number":["CARS"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"LOEWE DRUID","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"name":"Fraunhofer Internal Program","award":["Anti-Corona 840260 (DRECOR)"],"award-info":[{"award-number":["Anti-Corona 840260 (DRECOR)"]}]},{"name":"Fraunhofer Cluster of Excellence Immune mediated diseases (CIMD)","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]},{"name":"Reckitt Benckiser","award":["not applicable"],"award-info":[{"award-number":["not applicable"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2014including ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs)\u2014have 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.<\/jats:p>","DOI":"10.3390\/ijms23031049","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T08:20:57Z","timestamp":1642580457000},"page":"1049","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"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"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-2783","authenticated-orcid":false,"given":"Natasja","family":"de Bruin","sequence":"first","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany"},{"name":"Fraunhofer Cluster of Excellence Immune Mediated Diseases, CIMD, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Kathrin","family":"Schneider","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Reus","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt\/Main, Goethe University, Paul-Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"},{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, 22525 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Talmon","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1802-7565","authenticated-orcid":false,"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany"},{"name":"Institute of Medical Virology, University Hospital Frankfurt\/Main, Goethe University, Paul-Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denisa","family":"Bojkova","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt\/Main, Goethe University, Paul-Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jindrich","family":"Cinatl","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University Hospital Frankfurt\/Main, Goethe University, Paul-Ehrlich-Str. 40, 60596 Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imran","family":"Lodhi","sequence":"additional","affiliation":[{"name":"Reckitt Healthcare Ltd., Dansom Lane South, Kingston Upon Hull HU8 7DS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Charlesworth","sequence":"additional","affiliation":[{"name":"Reckitt Healthcare Ltd., Dansom Lane South, Kingston Upon Hull HU8 7DS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Reckitt Healthcare Ltd., Dansom Lane South, Kingston Upon Hull HU8 7DS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Pennick","sequence":"additional","affiliation":[{"name":"Reckitt Healthcare Ltd., Dansom Lane South, Kingston Upon Hull HU8 7DS, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William F.","family":"Laughey","sequence":"additional","affiliation":[{"name":"Reckitt Healthcare Ltd., Dansom Lane South, Kingston Upon Hull HU8 7DS, UK"},{"name":"Health Professions Education Unit, Hull York Medical School, University of York, Heslington, York YO10 5DD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip","family":"Gribbon","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Discovery Research ScreeningPort, 22525 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-2286","authenticated-orcid":false,"given":"Aimo","family":"Kannt","sequence":"additional","affiliation":[{"name":"Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany"},{"name":"Fraunhofer Cluster of Excellence 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