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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Veröffentlicht in:International journal of molecular sciences Jg. 24; H. 4; S. 3972
Hauptverfasser: 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: Journal Article
Sprache:Englisch
Veröffentlicht: Switzerland MDPI AG 16.02.2023
MDPI
Schlagworte:
Analysis
Antiviral drugs
Cell culture
Cell growth
Communication
Coronaviruses
Cytotoxicity
Enzymes
Genomes
Health aspects
Hepatitis C
HIV
Human immunodeficiency virus
Immunization
Infections
Patients
Protease inhibitors
Proteases
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Viruses
Germany
cell line specificity pyridyl indole carboxylates
protease inhibitors
SARS-CoV-2
peptidomimetics
azapeptide nitriles
ISSN:1422-0067, 1661-6596, 1422-0067
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Zusammenfassung: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.
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Present address: Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, University of Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24043972