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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-03038-8 |
| _version_ | 1818749459017760768 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T04:04:07Z |
| format | Article |
| id | doaj.art-5d7e140debe44068a932d7d7642b5a5f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T04:04:07Z |
| publishDate | 2017-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5d7e140debe44068a932d7d7642b5a5f2022-12-21T21:21:38ZengNature PortfolioScientific Reports2045-23222017-06-01711910.1038/s41598-017-03038-8De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domainChristina Calmels0Michel Ventura1Cindy Aknin2Mathieu Métifiot3Marie-Line Andreola4Univ. Bordeaux, CNRS, MFP, UMR 5234, 146 rue Léo SaignatUniv. Bordeaux, CNRS, MFP, UMR 5234, 146 rue Léo SaignatUniv. Bordeaux, CNRS, MFP, UMR 5234, 146 rue Léo SaignatUniv. Bordeaux, CNRS, MFP, UMR 5234, 146 rue Léo SaignatUniv. Bordeaux, CNRS, MFP, UMR 5234, 146 rue Léo SaignatAbstract 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.https://doi.org/10.1038/s41598-017-03038-8 |
| spellingShingle | Christina Calmels Michel Ventura Cindy Aknin Mathieu Métifiot Marie-Line Andreola De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-03038-8 |
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