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A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases
Positive-sense single-stranded RNA (+RNA) viruses have proven to be important pathogens that are able to threaten and deeply damage modern societies, as illustrated by the ongoing COVID-19 pandemic. Therefore, compounds active against most or many +RNA viruses are urgently needed. Here, we present P...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953834/ https://www.ncbi.nlm.nih.gov/pubmed/35335258 http://dx.doi.org/10.3390/molecules27061894 |
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author | Konkolova, Eva Krejčová, Kateřina Eyer, Luděk Hodek, Jan Zgarbová, Michala Fořtová, Andrea Jirasek, Michael Teply, Filip Reyes-Gutierrez, Paul E. Růžek, Daniel Weber, Jan Boura, Evzen |
author_facet | Konkolova, Eva Krejčová, Kateřina Eyer, Luděk Hodek, Jan Zgarbová, Michala Fořtová, Andrea Jirasek, Michael Teply, Filip Reyes-Gutierrez, Paul E. Růžek, Daniel Weber, Jan Boura, Evzen |
author_sort | Konkolova, Eva |
collection | PubMed |
description | Positive-sense single-stranded RNA (+RNA) viruses have proven to be important pathogens that are able to threaten and deeply damage modern societies, as illustrated by the ongoing COVID-19 pandemic. Therefore, compounds active against most or many +RNA viruses are urgently needed. Here, we present PR673, a helquat-like compound that is able to inhibit the replication of SARS-CoV-2 and tick-borne encephalitis virus in cell culture. Using in vitro polymerase assays, we demonstrate that PR673 inhibits RNA synthesis by viral RNA-dependent RNA polymerases (RdRps). Our results illustrate that the development of broad-spectrum non-nucleoside inhibitors of RdRps is feasible. |
format | Online Article Text |
id | pubmed-8953834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89538342022-03-26 A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases Konkolova, Eva Krejčová, Kateřina Eyer, Luděk Hodek, Jan Zgarbová, Michala Fořtová, Andrea Jirasek, Michael Teply, Filip Reyes-Gutierrez, Paul E. Růžek, Daniel Weber, Jan Boura, Evzen Molecules Article Positive-sense single-stranded RNA (+RNA) viruses have proven to be important pathogens that are able to threaten and deeply damage modern societies, as illustrated by the ongoing COVID-19 pandemic. Therefore, compounds active against most or many +RNA viruses are urgently needed. Here, we present PR673, a helquat-like compound that is able to inhibit the replication of SARS-CoV-2 and tick-borne encephalitis virus in cell culture. Using in vitro polymerase assays, we demonstrate that PR673 inhibits RNA synthesis by viral RNA-dependent RNA polymerases (RdRps). Our results illustrate that the development of broad-spectrum non-nucleoside inhibitors of RdRps is feasible. MDPI 2022-03-15 /pmc/articles/PMC8953834/ /pubmed/35335258 http://dx.doi.org/10.3390/molecules27061894 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Konkolova, Eva Krejčová, Kateřina Eyer, Luděk Hodek, Jan Zgarbová, Michala Fořtová, Andrea Jirasek, Michael Teply, Filip Reyes-Gutierrez, Paul E. Růžek, Daniel Weber, Jan Boura, Evzen A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title | A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title_full | A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title_fullStr | A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title_full_unstemmed | A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title_short | A Helquat-like Compound as a Potent Inhibitor of Flaviviral and Coronaviral Polymerases |
title_sort | helquat-like compound as a potent inhibitor of flaviviral and coronaviral polymerases |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8953834/ https://www.ncbi.nlm.nih.gov/pubmed/35335258 http://dx.doi.org/10.3390/molecules27061894 |
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