{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:19:00Z","timestamp":1791433140290,"version":"4.3.3"},"posted":{"date-parts":[[2024,4,29]]},"group-title":"Biophysics","reference-count":61,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["Research reported in this publication was supported in part by NIAID of the National Institute of Health under award number U19AI171399. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health"],"award-info":[{"award-number":["Research reported in this publication was supported in part by NIAID of the National Institute of Health under award number U19AI171399. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,9,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The Zika virus (ZIKV), discovered in Africa in 1947, swiftly spread across continents, causing significant concern due to its recent association with microcephaly in newborns and Guillain-Barr\u00e9 syndrome in adults. Despite a decrease in prevalence, the potential for a resurgence remains, necessitating urgent therapeutic interventions. Like other flaviviruses, ZIKV presents promising drug targets within its replication machinery, notably the NS3 helicase (NS3\n                  <jats:sup>Hel<\/jats:sup>\n                  ) protein, which plays critical roles in viral replication. However, a lack of structural information impedes the development of specific inhibitors targeting NS3\n                  <jats:sup>Hel<\/jats:sup>\n                  . Here we applied high-throughput crystallographic fragment screening on ZIKV NS3\n                  <jats:sup>Hel<\/jats:sup>\n                  , which yielded structures that reveal 3D binding poses of 46 fragments at multiple sites of the protein, including 11 unique fragments in the RNA-cleft site. These fragment structures provide templates for direct design of hit compounds and should thus assist the development of novel direct-acting antivirals against ZIKV and related flaviviruses, thus opening a promising avenue for combating future outbreaks.\n                <\/jats:p>","DOI":"10.1101\/2024.04.27.591279","type":"posted-content","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T18:20:16Z","timestamp":1714414816000},"source":"Crossref","is-referenced-by-count":2,"title":["High-throughput crystallographic fragment screening of Zika virus NS3 Helicase"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0613-9164","authenticated-orcid":false,"given":"Andre Schutzer","family":"Godoy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charline","family":"Giroud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalya C. M. 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