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-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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

International journal of molecular sciences - 23(2022), 3 vom: 19. Jan.

Sprache:

Englisch

Beteiligte Personen:

de Bruin, Natasja [VerfasserIn]
Schneider, Ann-Kathrin [VerfasserIn]
Reus, Philipp [VerfasserIn]
Talmon, Sonja [VerfasserIn]
Ciesek, Sandra [VerfasserIn]
Bojkova, Denisa [VerfasserIn]
Cinatl, Jindrich [VerfasserIn]
Lodhi, Imran [VerfasserIn]
Charlesworth, Bruce [VerfasserIn]
Sinclair, Simon [VerfasserIn]
Pennick, Graham [VerfasserIn]
Laughey, William F [VerfasserIn]
Gribbon, Philip [VerfasserIn]
Kannt, Aimo [VerfasserIn]
Schiffmann, Susanne [VerfasserIn]

Links:

Volltext

Themen:

362O9ITL9D
5GRO578KLP
ACE protein expression
ACE2 activity
ACE2 mRNA expression
ACE2 protein, human
Ace2 protein, mouse
Acetaminophen
Angiotensin-Converting Enzyme 2
Anti-Inflammatory Agents, Non-Steroidal
EC 3.4.17.23
Etoricoxib
Flurbiprofen
Ibuprofen
Journal Article
NSAIDs
SARS-CoV-2 infection
WK2XYI10QM
WRX4NFY03R

Anmerkungen:

Date Completed 16.02.2022

Date Revised 19.02.2022

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms23031049

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM336950691