{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:32:32Z","timestamp":1788784352304,"version":"build-2803163510"},"reference-count":102,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Zika virus (ZIKV) causes severe neurological disease, including microcephaly and Guillain-Barr\u00e9 syndrome, through complex interactions with host cell proteins. This review synthesizes the 2015\u20132025 published literature on ZIKV-host protein interactions and their therapeutic targeting. ZIKV enters cells via multiple receptor pathways: adhesion receptors (DC-SIGN, Hsp70), high-affinity entry receptors (ITGB4, GRP78, NCAM1), internalization receptors (integrin \u03b1v\u03b25, sialic acid), and endosomal receptors (AXL, TIM-1, CD300a). Viral structural proteins direct virion assembly, while nonstructural proteins NS1\u2013NS5 suppress immune responses, remodel cellular membranes, and dysregulate gene expression. NS5 uniquely suppresses neurodevelopmental genes and disrupts ciliary function through nuclear localization, directly driving microcephaly pathogenesis. Therapeutic strategies include receptor antagonists, protease inhibitors, and polymerase inhibitors. However, receptor redundancy, viral protein multifunctionality, and pregnancy safety constraints limit clinical translation. This review identifies ZIKV-host protein interactions as therapeutic targets and highlights barriers to drug development.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1754465","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:47:14Z","timestamp":1770187634000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Zika virus and host protein interactions for understanding molecular mechanisms of pathogenesis and therapeutic development"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiaodong","family":"Han","sequence":"first","affiliation":[{"name":"College of Life Sciences, Inner Mongolia Agriculture University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansen","family":"Du","sequence":"additional","affiliation":[{"name":"Qingdao International Travel Healthcare Center, Qingdao Customs District","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Inner Mongolia Agriculture University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuqian","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Inner Mongolia Agriculture University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huamuzi","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Inner Mongolia Agriculture University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guihua","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Inner Mongolia Agriculture University","place":["Hohhot, Inner Mongolia, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolong","family":"Cong","sequence":"additional","affiliation":[{"name":"Chinese Academy of Inspection and Quarantine","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.meegid.2019.01.018","article-title":"ZIKA virus entry mechanisms in human cells","volume":"69","author":"Agrelli","year":"2019","journal-title":"Infect. 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