De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain

Abstract Mosquito- and tick-borne pathogens including Chikungunya, Dengue, Japanese encephalitis, West Nile, Yellow fever and Zika virus, represent a new economic and public health challenge. In the absence of effective vaccines and specific therapies, only supportive regimens are administrated for...

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Autores principales:	Christina Calmels, Michel Ventura, Cindy Aknin, Mathieu Métifiot, Marie-Line Andreola
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d7e140debe44068a932d7d7642b5a5f
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spelling	oai:doaj.org-article:5d7e140debe44068a932d7d7642b5a5f2021-12-02T16:06:49ZDe novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain10.1038/s41598-017-03038-82045-2322https://doaj.org/article/5d7e140debe44068a932d7d7642b5a5f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03038-8https://doaj.org/toc/2045-2322Abstract Mosquito- and tick-borne pathogens including Chikungunya, Dengue, Japanese encephalitis, West Nile, Yellow fever and Zika virus, represent a new economic and public health challenge. In the absence of effective vaccines and specific therapies, only supportive regimens are administrated for most of these infections. Thus, the development of a targeted therapy is mandatory to stop the rapid progression of these pathogens and preoccupant associated burdens such as Guillain-Barre syndrome, microcephaly. For this, it is essential to develop biochemical tools to help study and target key viral enzymes involved in replication such as helicase complexes, methyl-transferases and RNA-dependent RNA polymerases. Here, we show that a highly purified ZIKV polymerase domain is active in vitro. Importantly, we show that this isolated domain is capable of de novo synthesis of the viral genome and efficient elongation without terminal nucleotide transferase activity. Altogether, this isolated polymerase domain will be a precious tool to screen and optimize specific nucleoside and non-nucleoside inhibitors to fight against Zika infections.Christina CalmelsMichel VenturaCindy AkninMathieu MétifiotMarie-Line AndreolaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Christina Calmels Michel Ventura Cindy Aknin Mathieu Métifiot Marie-Line Andreola De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
description	Abstract Mosquito- and tick-borne pathogens including Chikungunya, Dengue, Japanese encephalitis, West Nile, Yellow fever and Zika virus, represent a new economic and public health challenge. In the absence of effective vaccines and specific therapies, only supportive regimens are administrated for most of these infections. Thus, the development of a targeted therapy is mandatory to stop the rapid progression of these pathogens and preoccupant associated burdens such as Guillain-Barre syndrome, microcephaly. For this, it is essential to develop biochemical tools to help study and target key viral enzymes involved in replication such as helicase complexes, methyl-transferases and RNA-dependent RNA polymerases. Here, we show that a highly purified ZIKV polymerase domain is active in vitro. Importantly, we show that this isolated domain is capable of de novo synthesis of the viral genome and efficient elongation without terminal nucleotide transferase activity. Altogether, this isolated polymerase domain will be a precious tool to screen and optimize specific nucleoside and non-nucleoside inhibitors to fight against Zika infections.
format	article
author	Christina Calmels Michel Ventura Cindy Aknin Mathieu Métifiot Marie-Line Andreola
author_facet	Christina Calmels Michel Ventura Cindy Aknin Mathieu Métifiot Marie-Line Andreola
author_sort	Christina Calmels
title	De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
title_short	De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
title_full	De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
title_fullStr	De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
title_full_unstemmed	De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain
title_sort	de novo rna synthesis catalyzed by the zika virus rna polymerase domain
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d7e140debe44068a932d7d7642b5a5f
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De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain

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