TY  - JOUR
A1  - Reus, Philipp
A1  - Schneider, Ann-Kathrin
A1  - Ulshöfer, Thomas
A1  - Henke, Marina
A1  - Bojkova, Denisa
A1  - Cinatl, Jindrich
A1  - Ciesek, Sandra
A1  - Geisslinger, Gerd
A1  - Laux, Volker
A1  - Grättinger, Mira
A1  - Gribbon, Philip
A1  - Schiffmann, Susanne
T1  - 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
T2  - Life
N2  - 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.
KW  - ACE inhibitor
KW  - AT1 receptor antagonist
KW  - SARS-CoV-2
KW  - cell barrier integrity
Y1  - 2021
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62197
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-621970
SN  - 2075-1729
N1  - 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).
VL  - 11.2021
IS  - 8, art. 810
SP  - 1
EP  - 13
PB  - MDPI
CY  - Basel
ER  -