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.
- Geiger, N.
- Diesendorf, V.
- Roll, V.
- König, E. M.
- Obernolte, H.
- Sewald, K.
- Breidenbach, J.
- Pillaiyar, T.
- Gütschow, M.
- Müller, C. E.
- Bodem, J.
Keywords
- SARS-CoV-2
- azapeptide nitriles
- cell line specificity pyridyl indole carboxylates
- peptidomimetics
- protease inhibitors
