TY  - JOUR
A1  - Geiger, Nina
A1  - Diesendorf, Viktoria
A1  - Roll, Valeria
A1  - König, Eva-Maria
A1  - Obernolte, Helena
A1  - Sewald, Katherina
A1  - Breidenbach, Julian
A1  - Pillaiyar, Thanigaimalai
A1  - Gütschow, Michael
A1  - Müller, Christa E.
A1  - Bodem, Jochen
T1  - Cell type-specific anti-viral effects of novel SARS-CoV-2 main protease inhibitors
JF  - International Journal of Molecular Sciences
N2  - Recently, we have described novel pyridyl indole esters and peptidomimetics as potent inhibitors of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) main protease. Here, we analysed the impact of these compounds on viral replication. It has been shown that some antivirals against SARS-CoV-2 act in a cell line-specific way. Thus, the compounds were tested in Vero, Huh-7, and Calu-3 cells. We showed that the protease inhibitors at 30 µM suppress viral replication by up to 5 orders of magnitude in Huh-7 cells, while in Calu-3 cells, suppression by 2 orders of magnitude was achieved. Three pyridin-3-yl indole-carboxylates inhibited viral replication in all cell lines, indicating that they might repress viral replication in human tissue as well. Thus, we investigated three compounds in human precision-cut lung slices and observed donor-dependent antiviral activity in this patient-near system. Our results provide evidence that even direct-acting antivirals may act in a cell line-specific manner.
KW  - SARS-CoV-2
KW  - protease inhibitors
KW  - cell line specificity pyridyl indole carboxylates
KW  - azapeptide nitriles
KW  - peptidomimetics
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304034
SN  - 1422-0067
VL  - 24
IS  - 4
ER  -