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The entry of dengue virus into a host cell is mediated by its major envelope (E) protein. The crystal structure of the E protein reveals a hydrophobic pocket that is presumably important for low-pH-mediated membrane fusion. High-throughput docking with this hydrophobic pocket was performed, and hits were evaluated in cell-based assays. Compound 6 was identified as one of the inhibitors and had an average 50% effective concentration of 119 nM against dengue virus serotype 2 in a human cell line. Mechanism-of-action studies demonstrated that compound 6 acts at an early stage during dengue virus infection. It arrests dengue virus in vesicles that colocalize with endocytosed dextran and inhibits NS3 expression. The inhibitors described in this report can serve as molecular probes for the study of the entry of flavivirus into host cells.<\/jats:p>","DOI":"10.1128\/aac.01148-08","type":"journal-article","created":{"date-parts":[[2009,2,18]],"date-time":"2009-02-18T09:19:54Z","timestamp":1234948794000},"page":"1823-1831","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":196,"title":["A Small-Molecule Dengue Virus Entry Inhibitor"],"prefix":"10.1128","volume":"53","author":[{"given":"Qing-Yin","family":"Wang","sequence":"first","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejal J.","family":"Patel","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Vangrevelinghe","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel CH4002, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao Ying","family":"Xu","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranga","family":"Rao","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deana","family":"Jaber","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter","family":"Schul","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Gu","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Heudi","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngai Ling","family":"Ma","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mee Kian","family":"Poh","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Yee","family":"Phong","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H.","family":"Keller","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar","family":"Jacoby","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research, Basel CH4002, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash G.","family":"Vasudevan","sequence":"additional","affiliation":[{"name":"Novartis Institute for Tropical Diseases, Singapore 138670, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043382729"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.28.2.207"},{"key":"e_1_3_2_4_2","unstructured":"World Intellectual Property Organization 2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.7972"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69006-5"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.201392898"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.70.1.777"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.19.10528-10536.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199905)20:7<720::AID-JCC7>3.0.CO;2-X"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(05)64007-9"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/0166-3542(92)90060-I","volume":"18","year":"1992","unstructured":"Hollingshead, M. 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