Characterization of ACE inhibitors and AT1R antagonists with regard to their effect on ACE2 expression and infection with SARS-CoV-2 using a Caco-2 cell model

  • Blood-pressure-lowering drugs are proposed to foster SARS-CoV-2 infection by pharmacological upregulation of angiotensin-converting enzyme 2 (ACE2), the binding partner of the virus spike (S) protein, located on the surface of the host cells. Conversely, it is postulated that angiotensin–renin system antagonists may prevent lung damage caused by SARS-CoV-2 infection, by reducing angiotensin II levels, which can induce permeability of lung endothelial barrier via its interaction with the AT1 receptor (AT1R). Methods: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT1 antagonists (telmisartan, olmesartan) on the level of ACE2 mRNA and protein expression as well as their influence on the cytopathic effect of SARS-CoV-2 and on the cell barrier integrity in a Caco-2 cell model. Results: The drugs revealed no effect on ACE2 mRNA and protein expression. ACE inhibitors and AT1R antagonist olmesartan did not influence the infection rate of SARS-CoV-2 and were unable to prevent the SARS-CoV-2-induced cell barrier disturbance. A concentration of 25 µg/mL telmisartan significantly reduced the virus replication rate. Conclusion: ACE inhibitors and AT1R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.

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Author:Philipp ReusORCiD, Ann-Kathrin SchneiderGND, Thomas Ulshöfer, Marina HenkeORCiD, Denisa BojkovaORCiDGND, Jindrich CinatlORCiDGND, Sandra CiesekORCiDGND, Gerd GeisslingerORCiDGND, Volker LauxORCiD, Mira GrättingerORCiDGND, Philip GribbonORCiD, Susanne SchiffmannORCiDGND
Parent Title (English):Life
Place of publication:Basel
Document Type:Article
Date of Publication (online):2021/08/10
Date of first Publication:2021/08/10
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/04
Tag:ACE inhibitor; AT1 receptor antagonist; SARS-CoV-2; cell barrier integrity
Issue:8, art. 810
Article Number:810
Page Number:13
First Page:1
Last Page:13
This work was supported by the BMBF (project CARS; funding code 01KI20179), the Landesoffensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz (LOEWE), Centre Translationale Medizin und Pharmakologie (TMP), the LOEWE Centre Novel Drug Targets against Poverty-Related and Neglected Tropical Infectious Diseases (DRUID), the LOEWE Centre Translational Biodiversity Genomics (TBG), the Fraunhofer Internal Program under Grant No. Anti-Corona 840260 (DRECOR) and the Fraunhofer Cluster of Excellence Immune mediated diseases (CIMD).
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0