{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T23:01:35Z","timestamp":1793055695428,"version":"4.5.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2020,10,14]],"date-time":"2020-10-14T00:00:00Z","timestamp":1602633600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001381","name":"National Research Foundation Singapore","doi-asserted-by":"publisher","award":["NRF2016-CRP001-063"],"award-info":[{"award-number":["NRF2016-CRP001-063"]}],"id":[{"id":"10.13039\/501100001381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2020,10,14]]},"abstract":"<jats:p>\n            Zika virus belongs to the\n            <jats:italic>Flavivirus<\/jats:italic>\n            genus, which comprises several important human pathogens. There is currently neither an approved vaccine nor antiviral drugs available to prevent infection by ZIKV. The nonstructural protein 5 (NS5) polymerase, which is responsible for replicating the viral RNA genome, represents one of the most promising targets for antiviral drug development. Starting from compounds recently developed against dengue virus NS5, we designed and synthesized inhibitors targeting Zika virus NS5. We show that these novel compounds inhibit viral replication by targeting the polymerase activity. High-resolution X-ray crystallographic structures of protein-inhibitor complexes demonstrated specific binding to an allosteric site within the polymerase, called the N pocket. This work paves the way for the future structure-based design of potent compounds specifically targeting ZIKV RNA polymerase activity.\n          <\/jats:p>","DOI":"10.1128\/jvi.00794-20","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T13:23:26Z","timestamp":1597065806000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":54,"title":["Non-nucleoside Inhibitors of Zika Virus RNA-Dependent RNA Polymerase"],"prefix":"10.1128","volume":"94","author":[{"given":"Aicha","family":"Gharbi-Ayachi","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sridhar","family":"Santhanakrishnan","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yee Hwa","family":"Wong","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitti W. K.","family":"Chan","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siok Thing","family":"Tan","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roderick W.","family":"Bates","sequence":"additional","affiliation":[{"name":"School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-3831","authenticated-orcid":false,"given":"Subhash G.","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore"},{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-686X","authenticated-orcid":false,"given":"Abbas","family":"El Sahili","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Lescar","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University, Singapore"},{"name":"Nanyang Institute of Structural Biology, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60238-X"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES2014.19.9.20720"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.15831"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31450-2"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/v8120322"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.01.007"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/v9040091"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02283-06"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.06.007"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.04.010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.03.007"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004682"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1600651"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00006-4"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907010106"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02451-09"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2013.09.013"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005737"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201696241"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14764"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2053230X17001601"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14763"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2017.01.020"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/35065653"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky473"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00045-13"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2015.04.007"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1177\/1087057110389323"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2017.1313175"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2019.07.010"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444909047337"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218231"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00794-20","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00794-20","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:59:53Z","timestamp":1646492393000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00794-20"}},"subtitle":[],"editor":[{"given":"Mark T.","family":"Heise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2020,10,14]]},"references-count":33,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2020,10,14]]}},"alternative-id":["10.1128\/JVI.00794-20"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00794-20","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,14]]},"assertion":[{"value":"2020-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e00794-20"}}