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 syste...

Full description

Saved in:
Bibliographic Details
Published in:Life (Basel, Switzerland) Switzerland), 2021-08, Vol.11 (8), p.810
Main Authors: Reus, Philipp, Schneider, Ann-Kathrin, Ulshöfer, Thomas, Henke, Marina, Bojkova, Denisa, Cinatl, Jindrich, Ciesek, Sandra, Geisslinger, Gerd, Laux, Volker, Grättinger, Mira, Gribbon, Philip, Schiffmann, Susanne
Format: Article
Language:English
Subjects:
ACE inhibitor
ACE2
Angiotensin II
Angiotensin-converting enzyme 2
Angiotensin-converting enzyme inhibitors
Antagonists
Antibodies
AT1 receptor antagonist
Blood pressure
Captopril
cell barrier integrity
Coronaviruses
COVID-19
Cytotoxicity
Damage prevention
Drugs
Gene expression
Hypertension
Infections
Inhibitors
Integrity
Lungs
Membranes
mRNA
Peptidyl-dipeptidase A
Permeability
Pharmacology
Protein expression
Proteins
Renin
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Viral diseases
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2075-1729
2075-1729
DOI:10.3390/life11080810