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.show moreshow less

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Metadaten
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
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):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International