Cell Type-Specific Anti-Viral Effects of Novel SARS-CoV-2 Main Protease Inhibitors

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 agains...

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Bibliographic Details
Published in:International journal of molecular sciences 2023-02, Vol.24 (4), p.3972
Main Authors: Geiger, Nina, Diesendorf, Viktoria, Roll, Valeria, König, Eva-Maria, Obernolte, Helena, Sewald, Katherina, Breidenbach, Julian, Pillaiyar, Thanigaimalai, Gütschow, Michael, Müller, Christa E, Bodem, Jochen
Format: Article
Language:English
Subjects:
Analysis
Antiviral activity
Antiviral agents
Carboxylates
Cell culture
Cell growth
Cell lines
Communication
Coronaviruses
Cytotoxicity
Enzymes
Esters
Genomes
Health aspects
Hepatitis C
HIV
Human immunodeficiency virus
Human tissues
Immunization
Impact analysis
Infections
Patients
Peptidomimetics
Protease
Protease inhibitors
Proteases
Proteinase inhibitors
Replication
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Viruses
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24043972