{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:09:42Z","timestamp":1790806182427,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,2]],"date-time":"2021-01-02T00:00:00Z","timestamp":1609545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["37155"],"award-info":[{"award-number":["37155"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN-2017-04003"],"award-info":[{"award-number":["RGPIN-2017-04003"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Flavivirus genus includes many deadly viruses such as the Japanese encephalitis virus (JEV) and Zika virus (ZIKV). The 5\u2032 terminal regions (TR) of flaviviruses interact with human proteins and such interactions are critical for viral replication. One of the human proteins identified to interact with the 5\u2032 TR of JEV is the DEAD-box helicase, DDX3X. In this study, we in vitro transcribed the 5\u2032 TR of JEV and demonstrated its direct interaction with recombinant DDX3X (Kd of 1.66 \u00b1 0.21 \u00b5M) using microscale thermophoresis (MST). Due to the proposed structural similarities of 5\u2032 and 3\u2032 TRs of flaviviruses, we investigated if the ZIKV 5\u2032 TR could also interact with human DDX3X. Our MST studies suggested that DDX3X recognizes ZIKV 5\u2032 TR with a Kd of 7.05 \u00b1 0.75 \u00b5M. Next, we performed helicase assays that suggested that the binding of DDX3X leads to the unwinding of JEV and ZIKV 5\u2032 TRs. Overall, our data indicate, for the first time, that DDX3X can directly bind and unwind in vitro transcribed flaviviral TRs. In summary, our work indicates that DDX3X could be further explored as a therapeutic target to inhibit Flaviviral replication<\/jats:p>","DOI":"10.3390\/ijms22010413","type":"journal-article","created":{"date-parts":[[2021,1,3]],"date-time":"2021-01-03T19:54:46Z","timestamp":1609703686000},"page":"413","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Human DDX3X Unwinds Japanese Encephalitis and Zika Viral 5\u2032 Terminal Regions"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6604-8566","authenticated-orcid":false,"given":"Corey","family":"Nelson","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1077-9682","authenticated-orcid":false,"given":"Tyler","family":"Mrozowich","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-9063","authenticated-orcid":false,"given":"Darren L.","family":"Gemmill","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1334-9247","authenticated-orcid":false,"given":"Sean M.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0627-2923","authenticated-orcid":false,"given":"Trushar R.","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada"},{"name":"Department of Microbiology, Immunology and Infectious Disease, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 1N4, Canada"},{"name":"Li Ka Shing Institute of Virology and Discovery Lab, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,2]]},"reference":[{"key":"ref_1","unstructured":"Chambers, T.J., and Monath, T.P. 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