{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T07:37:43Z","timestamp":1759563463217,"version":"3.37.3"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,2]],"date-time":"2017-06-02T00:00:00Z","timestamp":1496361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 <jats:italic>in vitro<\/jats:italic>. Importantly, we show that this isolated domain is capable of <jats:italic>de novo<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-03038-8","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T09:54:09Z","timestamp":1495792449000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["De novo RNA synthesis catalyzed by the Zika Virus RNA polymerase domain"],"prefix":"10.1038","volume":"7","author":[{"given":"Christina","family":"Calmels","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Ventura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cindy","family":"Aknin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8103-9120","authenticated-orcid":false,"given":"Mathieu","family":"M\u00e9tifiot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Line","family":"Andreola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,6,2]]},"reference":[{"key":"3038_CR1","doi-asserted-by":"publisher","first-page":"h6983","DOI":"10.1136\/bmj.h6983","volume":"351","author":"O Dyer","year":"2015","unstructured":"Dyer, O. Zika virus spreads across Americas as concerns mount over birth defects. BMJ \n                           351, h6983, doi:10.1136\/bmj.h6983 (2015).","journal-title":"BMJ"},{"key":"3038_CR2","doi-asserted-by":"publisher","first-page":"20720","DOI":"10.2807\/1560-7917.ES2014.19.9.20720","volume":"19","author":"E Oehler","year":"2014","unstructured":"Oehler, E. et al. Zika virus infection complicated by Guillain-Barr\u00e9 syndrome \u2013 case report, French Polynesia, December 2013. Eurosurveillance \n                           19, 20720, doi:10.2807\/1560-7917.ES2014.19.9.20720 (2014).","journal-title":"Eurosurveillance"},{"key":"3038_CR3","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.jcv.2016.08.297","volume":"83","author":"CN Soares","year":"2016","unstructured":"Soares, C. N. et al. Fatal encephalitis associated with Zika virus infection in an adult. J. Clin. Virol. \n                           83, 63\u201365, doi:10.1016\/j.jcv.2016.08.297 (2016).","journal-title":"J. Clin. Virol."},{"key":"3038_CR4","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1128\/CMR.00014-16","volume":"29","author":"A Panchaud","year":"2016","unstructured":"Panchaud, A., Stojanov, M., Ammerdorffer, A., Vouga, M. & Baud, D. Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes. Clin. Microbiol. Rev. \n                           29, 659\u2013694, doi:10.1128\/CMR.00014-16 (2016).","journal-title":"Clin. Microbiol. Rev."},{"doi-asserted-by":"publisher","unstructured":"\u0160trafela, P. et al. Zika Virus\u2013Associated Micrencephaly: A Thorough Description of Neuropathologic Findings in the Fetal Central Nervous System. Arch. Pathol. Lab. Med., doi:10.5858\/arpa.2016-0341-SA (2016).","key":"3038_CR5","DOI":"10.5858\/arpa.2016-0341-SA"},{"unstructured":"Publication Details | 1 December 2015: Neurological syndrome, congenital malformations, and Zika virus infection. Implications for public health in the Americas \u2013 Epidemiological Alert. Available at: http:\/\/www.paho.org\/hq\/index.php?option=com_docman&task=doc_details&gid=32405&Itemid=270&lang=en (Accessed: 18th October 2016) (2015).","key":"3038_CR6"},{"doi-asserted-by":"publisher","unstructured":"Zhang, Z. et al. Crystal structure of unlinked NS2B-NS3 protease from Zika virus. Science aai9309, doi:10.1126\/science.aai9309 (2016).","key":"3038_CR7","DOI":"10.1126\/science.aai9309"},{"key":"3038_CR8","doi-asserted-by":"publisher","first-page":"3097","DOI":"10.1016\/j.celrep.2016.08.091","volume":"16","author":"J Coloma","year":"2016","unstructured":"Coloma, J., Jain, R., Rajashankar, K. R., Garc\u00eda-Sastre, A. & Aggarwal, A. K. Structures of NS5 Methyltransferase from Zika Virus. Cell Rep. \n                           16, 3097\u20133102, doi:10.1016\/j.celrep.2016.08.091 (2016).","journal-title":"Cell Rep."},{"key":"3038_CR9","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1126\/science.aah3963","volume":"354","author":"BM Akiyama","year":"2016","unstructured":"Akiyama, B. M. et al. Zika virus produces noncoding RNAs using a multi-pseudoknot structure that confounds a cellular exonuclease. Science \n                           354, 1148\u20131152, doi:10.1126\/science.aah3963 (2016).","journal-title":"Science"},{"key":"3038_CR10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.antiviral.2016.11.020","volume":"137","author":"K Herc\u00edk","year":"2017","unstructured":"Herc\u00edk, K. et al. Adenosine triphosphate analogs can efficiently inhibit the Zika virus RNA-dependent RNA polymerase. Antiviral Res. \n                           137, 131\u2013133, doi:10.1016\/j.antiviral.2016.11.020 (2017).","journal-title":"Antiviral Res."},{"key":"3038_CR11","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.antiviral.2016.12.021","volume":"140","author":"S Potisopon","year":"2017","unstructured":"Potisopon, S., Ferron, F., Fattorini, V., Selisko, B. & Canard, B. Substrate selectivity of Dengue and Zika virus NS5 polymerase towards 2\u2032-modified nucleotide analogues. Antiviral Res. \n                           140, 25\u201336, doi:10.1016\/j.antiviral.2016.12.021 (2017).","journal-title":"Antiviral Res."},{"doi-asserted-by":"crossref","unstructured":"Xu, H.-T. et al. Purification of Zika virus RNA-dependent RNA polymerase and its use to identify small-molecule Zika inhibitors. J. Antimicrob. Chemother (2017).","key":"3038_CR12","DOI":"10.1093\/jac\/dkw514"},{"doi-asserted-by":"crossref","unstructured":"Lu, G. et al. Analysis of Ribonucleotide 5\u2032-Triphosphate Analogs as Potential Inhibitors of Zika Virus RNA-dependent RNA Polymerase Using Non-Radioactive Polymerase Assays. Antimicrob. Agents Chemother. 61, 01967\u201316 (2016).","key":"3038_CR13","DOI":"10.1128\/AAC.01967-16"},{"doi-asserted-by":"publisher","unstructured":"Sacramento, C. Q. et al. The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication. Sci. Rep. 7, 40920, doi:10.1038\/srep40920 (2017).","key":"3038_CR14","DOI":"10.1038\/srep40920"},{"key":"3038_CR15","doi-asserted-by":"publisher","first-page":"38448","DOI":"10.1074\/jbc.M607641200","volume":"281","author":"KJ Chappell","year":"2006","unstructured":"Chappell, K. J., Stoermer, M. J., Fairlie, D. P. & Young, P. R. Insights to Substrate Binding and Processing by West Nile Virus NS3 Protease through Combined Modeling, Protease Mutagenesis, and Kinetic Studies. J. Biol. 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The I-TASSER Suite: protein structure and function prediction. Nat. Methods \n                           12, 7\u20138, doi:10.1038\/nmeth.3213 (2015).","journal-title":"Nat. Methods"},{"key":"3038_CR19","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.antiviral.2016.11.023","volume":"137","author":"KM Bullard-Feibelman","year":"2017","unstructured":"Bullard-Feibelman, K. M. et al. The FDA-approved drug sofosbuvir inhibits Zika virus infection. Antiviral Res. \n                           137, 134\u2013140, doi:10.1016\/j.antiviral.2016.11.023 (2017).","journal-title":"Antiviral Res."},{"key":"3038_CR20","doi-asserted-by":"publisher","first-page":"e0004695","DOI":"10.1371\/journal.pntd.0004695","volume":"10","author":"J Zmurko","year":"2016","unstructured":"Zmurko, J. et al. The Viral Polymerase Inhibitor 7-Deaza-2\u2032- C -Methyladenosine Is a Potent Inhibitor of In Vitro Zika Virus Replication and Delays Disease Progression in a Robust Mouse Infection Model. PLOS Negl Trop Dis. \n                           10, e0004695, doi:10.1371\/journal.pntd.0004695 (2016).","journal-title":"PLOS Negl Trop Dis."},{"key":"3038_CR21","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1002\/jmv.24678","volume":"88","author":"AA Elfiky","year":"2016","unstructured":"Elfiky, A. A. Zika viral polymerase inhibition using anti-HCV drugs both in market and under clinical trials. J. Med. Virol. \n                           88, 2044\u20132051, doi:10.1002\/jmv.v88.12 (2016).","journal-title":"J. Med. Virol."},{"key":"3038_CR22","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1093\/infdis\/jiw226","volume":"214","author":"L Eyer","year":"2016","unstructured":"Eyer, L. et al. Nucleoside Inhibitors of Zika Virus. J. Infect. Dis. \n                           214, 707\u2013711, doi:10.1093\/infdis\/jiw226 (2016).","journal-title":"J. Infect. Dis."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03038-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03038-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03038-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T04:53:28Z","timestamp":1671771208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-03038-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,2]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["3038"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-03038-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"type":"electronic","value":"2045-2322"}],"subject":[],"published":{"date-parts":[[2017,6,2]]},"assertion":[{"value":"9 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 June 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"2697"}}