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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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