{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T23:33:54Z","timestamp":1788910434144,"version":"build-2803163510"},"reference-count":44,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,4,30]],"date-time":"2023-04-30T00:00:00Z","timestamp":1682812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35GM131881"],"award-info":[{"award-number":["R35GM131881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS105969-01"],"award-info":[{"award-number":["R01 NS105969-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R35GM131881"],"award-info":[{"award-number":["R35GM131881"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS105969-01"],"award-info":[{"award-number":["R01 NS105969-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barr\u00e9 syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the \u201csuper-open\u201d conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections.<\/jats:p>","DOI":"10.3390\/v15051106","type":"journal-article","created":{"date-parts":[[2023,5,1]],"date-time":"2023-05-01T12:02:31Z","timestamp":1682942551000},"page":"1106","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in \u201cSuper-Open\u201d Conformation"],"prefix":"10.3390","volume":"15","author":[{"given":"Ittipat","family":"Meewan","sequence":"first","affiliation":[{"name":"Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand"},{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey A.","family":"Shiryaev","sequence":"additional","affiliation":[{"name":"Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Kattoula","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Teng","family":"Huang","sequence":"additional","affiliation":[{"name":"Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5886-1047","authenticated-orcid":false,"given":"Vivian","family":"Lin","sequence":"additional","affiliation":[{"name":"Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao-Han","family":"Chuang","sequence":"additional","affiliation":[{"name":"Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4641-3997","authenticated-orcid":false,"given":"Alexey V.","family":"Terskikh","sequence":"additional","affiliation":[{"name":"Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben","family":"Abagyan","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.3201\/eid2110.150847","article-title":"Zika Virus Outbreak, Bahia, Brazil","volume":"21","author":"Campos","year":"2015","journal-title":"Emerg. 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