{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:58:46Z","timestamp":1791874726828,"version":"4.3.4"},"reference-count":34,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T00:00:00Z","timestamp":1537228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["T32GM007276"],"award-info":[{"award-number":["T32GM007276"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["Pioneer Award"],"award-info":[{"award-number":["Pioneer Award"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["U19AI109662"],"award-info":[{"award-number":["U19AI109662"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,10,2]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Inhibitors of dengue virus, a mosquito-borne pathogen, are urgently needed. Virally encoded NS2B\/3, a two-subunit serine proteinase, is responsible for many cleavages within the viral polyprotein. We demonstrate that two cleavage sites flanking NS3 and one that is internal are self-processing. This strict intramolecular cleavage dictates that, if uncleaved precursors can inhibit viral growth, this phenotype will be\n                    <jats:italic>trans<\/jats:italic>\n                    -dominant. Indeed, a mutation that abrogates one of the self-processing sites caused\n                    <jats:italic>trans<\/jats:italic>\n                    -dominant inhibition of wild-type virus. This site is also the most susceptible to a dengue proteinase inhibitor, providing a compelling rationale for its efficacy. We suggest that explicit targeting of specific intramolecular cleavage sites will be an effective antiviral strategy that can suppress multiple variants in an intracellular quasispecies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1805195115","type":"journal-article","created":{"date-parts":[[2018,9,18]],"date-time":"2018-09-18T12:07:41Z","timestamp":1537272461000},"page":"10136-10141","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":47,"title":["Targeting intramolecular proteinase NS2B\/3 cleavages for\n                    <i>trans<\/i>\n                    -dominant inhibition of dengue virus"],"prefix":"10.1073","volume":"115","author":[{"given":"David A.","family":"Constant","sequence":"first","affiliation":[{"name":"Department of Biology, Stanford University, Stanford, CA 94305;"},{"name":"Department of Genetics, Stanford University School of Medicine, Stanford, CA 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