{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:53:01Z","timestamp":1792511581703,"version":"4.5.0"},"reference-count":100,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zika virus (ZIKV; family, Flaviviridae), which causes congenital Zika syndrome, Guillain-Barr\u00e9 Syndrome, and other severe diseases, is transmitted mainly by mosquitoes; however, the virus can be transmitted through other routes. Among the three structural and seven nonstructural proteins, the surface envelope (E) protein of ZIKV plays a critical role in viral entry and pathogenesis, making it a key target for the development of effective entry inhibitors. This review article describes the life cycle, genome, and encoded proteins of ZIKV, illustrates the structure and function of the ZIKV E protein, summarizes E protein-targeting entry inhibitors (with a focus on those based on natural products and small molecules), and highlights challenges that may potentially hinder the development of effective inhibitors of ZIKV infection. Overall, the article will provide useful guidance for further development of safe and potent ZIKV entry inhibitors targeting the viral E protein.<\/jats:p>","DOI":"10.3390\/ijms25179424","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:39:32Z","timestamp":1725010772000},"page":"9424","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Envelope Protein-Targeting Zika Virus Entry Inhibitors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1593-037X","authenticated-orcid":false,"given":"Abhijeet","family":"Roy","sequence":"first","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7781-186X","authenticated-orcid":false,"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University, Ames, IA 50011, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2761-0506","authenticated-orcid":false,"given":"Asim K.","family":"Debnath","sequence":"additional","affiliation":[{"name":"Lindsey F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanying","family":"Du","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika Virus (I). 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