Cell type-specific anti-viral effects of novel SARS-CoV-2 main protease inhibitors
Please always quote using this URN: urn:nbn:de:bvb:20-opus-304034
- 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-3Recently, 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.…
Author: | Nina Geiger, Viktoria Diesendorf, Valeria Roll, Eva-Maria König, Helena Obernolte, Katherina Sewald, Julian Breidenbach, Thanigaimalai Pillaiyar, Michael Gütschow, Christa E. Müller, Jochen Bodem |
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URN: | urn:nbn:de:bvb:20-opus-304034 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Language: | English |
Parent Title (English): | International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Year of Completion: | 2023 |
Volume: | 24 |
Issue: | 4 |
Article Number: | 3972 |
Source: | International Journal of Molecular Sciences (2023) 24:4, 3972. https://doi.org/10.3390/ijms24043972 |
DOI: | https://doi.org/10.3390/ijms24043972 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Tag: | SARS-CoV-2; azapeptide nitriles; cell line specificity pyridyl indole carboxylates; peptidomimetics; protease inhibitors |
Release Date: | 2023/11/30 |
Date of first Publication: | 2023/02/16 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |