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Inhibition of Zika Virus Replication by Silvestrol

The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated fro...

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Autores principales: Elgner, Fabian, Sabino, Catarina, Basic, Michael, Ploen, Daniela, Grünweller, Arnold, Hildt, Eberhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923443/
https://www.ncbi.nlm.nih.gov/pubmed/29584632
http://dx.doi.org/10.3390/v10040149
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author Elgner, Fabian
Sabino, Catarina
Basic, Michael
Ploen, Daniela
Grünweller, Arnold
Hildt, Eberhard
author_facet Elgner, Fabian
Sabino, Catarina
Basic, Michael
Ploen, Daniela
Grünweller, Arnold
Hildt, Eberhard
author_sort Elgner, Fabian
collection PubMed
description The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted.
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spelling pubmed-59234432018-05-03 Inhibition of Zika Virus Replication by Silvestrol Elgner, Fabian Sabino, Catarina Basic, Michael Ploen, Daniela Grünweller, Arnold Hildt, Eberhard Viruses Article The Zika virus (ZIKV) outbreak in 2016 in South America with specific pathogenic outcomes highlighted the need for new antiviral substances with broad-spectrum activities to react quickly to unexpected outbreaks of emerging viral pathogens. Very recently, the natural compound silvestrol isolated from the plant Aglaia foveolata was found to have very potent antiviral effects against the (−)-strand RNA-virus Ebola virus as well as against Corona- and Picornaviruses with a (+)-strand RNA-genome. This antiviral activity is based on the impaired translation of viral RNA by the inhibition of the DEAD-box RNA helicase eukaryotic initiation factor-4A (eIF4A) which is required to unwind structured 5´-untranslated regions (5′-UTRs) of several proto-oncogenes and thereby facilitate their translation. Zika virus is a flavivirus with a positive-stranded RNA-genome harboring a 5′-capped UTR with distinct secondary structure elements. Therefore, we investigated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Two different ZIKV strains were used. In both infected A549 cells and primary human hepatocytes, silvestrol has the potential to exert a significant inhibition of ZIKV replication for both analyzed strains, even though the ancestor strain from Uganda is less sensitive to silvestrol. Our data might contribute to identify host factors involved in the control of ZIKV infection and help to develop antiviral concepts that can be used to treat a variety of viral infections without the risk of resistances because a host protein is targeted. MDPI 2018-03-27 /pmc/articles/PMC5923443/ /pubmed/29584632 http://dx.doi.org/10.3390/v10040149 Text en © 2018 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Elgner, Fabian
Sabino, Catarina
Basic, Michael
Ploen, Daniela
Grünweller, Arnold
Hildt, Eberhard
Inhibition of Zika Virus Replication by Silvestrol
title Inhibition of Zika Virus Replication by Silvestrol
title_full Inhibition of Zika Virus Replication by Silvestrol
title_fullStr Inhibition of Zika Virus Replication by Silvestrol
title_full_unstemmed Inhibition of Zika Virus Replication by Silvestrol
title_short Inhibition of Zika Virus Replication by Silvestrol
title_sort inhibition of zika virus replication by silvestrol
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5923443/
https://www.ncbi.nlm.nih.gov/pubmed/29584632
http://dx.doi.org/10.3390/v10040149
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