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 AT 1 receptor (AT 1 R). Methods: We have investigated the influence of the ACE inhibitors (lisinopril, captopril) and the AT 1 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 AT 1 R 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 AT 1 R antagonist showed neither beneficial nor detrimental effects on SARS-CoV-2-infection and cell barrier integrity in vitro at pharmacologically relevant concentrations.
【저자키워드】 SARS-CoV-2, ACE inhibitor, AT1 receptor antagonist, cell barrier integrity, 【초록키워드】 ACE2, SARS-COV-2 infection, drug, in vitro, angiotensin-converting enzyme 2, Protein, virus replication, receptor, infection rate, binding, Cytopathic effect, Interaction, Concentration, Caco-2, lung damage, host cells, ACE2 mRNA, upregulation, protein expression, lung endothelial, Virus spike, pharmacological, antagonist, Prevent, Cell, concentrations, caused, significantly, investigated, reduced, reducing, induce, detrimental effect, 【제목키워드】 ACE2, Model, ACE, Caco-2, characterization, antagonist, Effect,