{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:00:06Z","timestamp":1787022006760,"version":"build-2736575974"},"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T00:00:00Z","timestamp":1499644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["R-154-002-580-112"],"award-info":[{"award-number":["R-154-002-580-112"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001459","name":"Ministry of Education - Singapore","doi-asserted-by":"publisher","award":["MOE2015-T2-1-111"],"award-info":[{"award-number":["MOE2015-T2-1-111"]}],"id":[{"id":"10.13039\/501100001459","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0180632","type":"journal-article","created":{"date-parts":[[2017,7,10]],"date-time":"2017-07-10T13:39:46Z","timestamp":1499693986000},"page":"e0180632","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":97,"title":["Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants"],"prefix":"10.1371","volume":"12","author":[{"given":"Amrita","family":"Roy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liangzhong","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shagun","family":"Srivastava","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0224-6322","authenticated-orcid":true,"given":"Jianxing","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,7,10]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.jinf.2016.02.011","article-title":"Zika fever and congenital Zika syndrome: an unexpected emerging arboviral disease","volume":"72","author":"JF Chan","year":"2016","journal-title":"J Infect"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/jmv.24563","article-title":"Zika virus: an update on epidemiology, pathology, molecular biology, and animal model","volume":"88","author":"S Ramos da Silva","year":"2016","journal-title":"J Med Virol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/0035-9203(52)90042-4","article-title":"Zika virus (I). Isolations and serological specificity","volume":"46","author":"G Dick","year":"1952","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"e119","DOI":"10.1016\/S1473-3099(16)30010-X","article-title":"Zika virus: history of a newly emerging arbovirus","volume":"16","author":"N Wikan","year":"2016","journal-title":"Lancet Infect Diseas"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"e00500","DOI":"10.1128\/genomeA.00500-14","article-title":"Complete coding sequence of Zika virus from a French Polynesia outbreak in 2013","volume":"2","author":"C Baronti","year":"2014","journal-title":"Genome Announc"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1016\/S1473-3099(16)30270-5","article-title":"Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study","volume":"16","author":"II Bogoch","year":"2016","journal-title":"Lancet Infect Diseas"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa1600651","article-title":"Zika virus associated with microcephaly","volume":"2016","author":"J Mlakar","year":"2016","journal-title":"New Engl J Med"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1056\/NEJMc1604449","article-title":"Evidence of sexual transmission of Zika virus","volume":"374","author":"E D\u2019Ortenzio","year":"2016","journal-title":"New Eng J Medi"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.stem.2016.04.017","article-title":"Zika virus disrupts neural progenitor development and leads to microcephaly in mice","volume":"19","author":"C Li","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/nature18296","article-title":"The Brazilian Zika virus strain causes birth defects in experimental models","volume":"534","author":"FR Cugola","year":"2016","journal-title":"Nature"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1126\/science.352.6292.1375","article-title":"Experts fear Zika\u2019s effects may be even worse than thought","volume":"352","author":"G Vogel","year":"2016","journal-title":"Science"},{"key":"ref12","article-title":"Zika virus infection associated with severe thrombocytopenia","author":"TM Sharp","year":"2016","journal-title":"Clin Diseas"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4103\/0974-777X.176140","article-title":"The emergence of Zika virus as a global health security threat: a review and a consensus statement of the INDUSEM Joint Working Group (JWG)","volume":"8","author":"V Sikka","year":"2016","journal-title":"J Glob Infect Disea"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.ebiom.2016.11.017","article-title":"Zika Virus Infection in Dexamethasone-immunosuppressed Mice Demonstrating Disseminated Infection with Multi-organ Involvement Including Orchitis Effectively Treated by Recombinant Type I Interferons","volume":"14","author":"JF-W Chan","year":"2016","journal-title":"EBioMedicine"},{"key":"ref15","unstructured":"Organization WH. WHO statement on the first meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on ZIKV and observed increase in neurological disorders and neonatal malformations. [Internet]. 2016 [cited 30 Sep 2016]. <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.who.int\/mediacentre\/news\/statements\/2016\/1st-emergency-committee-zika\/en\/\" xlink:type=\"simple\">www.who.int\/mediacentre\/news\/statements\/2016\/1st-emergency-committee-zika\/en\/<\/ext-link>"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1177\/2040206616653873","article-title":"Predicting Zika virus structural biology: Challenges and opportunities for intervention","volume":"24","author":"BD Cox","year":"2015","journal-title":"Antivir Chem Chemother"},{"key":"ref17","article-title":"Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus","author":"W Dejnirattisai","year":"2016","journal-title":"Nat Immunol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20564","article-title":"Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice","volume":"540","author":"G Sapparapu","year":"2016","journal-title":"Nature"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika virus envelope protein and its complex with a flavivirus broadly protective antibody","volume":"19","author":"L Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"14722","DOI":"10.1038\/ncomms14722","article-title":"A human antibody against Zika virus crosslinks the E protein to prevent infection","volume":"8","author":"SS Hasan","year":"2017","journal-title":"Nat Comm"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"e0134823","DOI":"10.1371\/journal.pone.0134823","article-title":"NMR and MD Studies Reveal That the Isolated Dengue NS3 Protease Is an Intrinsically Disordered Chymotrypsin Fold Which Absolutely Requests NS2B for Correct Folding and Functional Dynamics","volume":"10","author":"G Gupta","year":"2015","journal-title":"PloS One"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.mi.44.100190.003245","article-title":"Flavivirus genome organization, expression, and replication","volume":"44","author":"TJ Chambers","year":"1990","journal-title":"Annu Rev Microbiol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"45762","DOI":"10.1074\/jbc.M107360200","article-title":"Activity of recombinant dengue 2 virus NS3 protease in the presence of a truncated NS2B co-factor, small peptide substrates, and inhibitors","volume":"276","author":"D Leung","year":"2001","journal-title":"J Biol Chem"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.antiviral.2017.03.011","article-title":"Solution conformations of a linked construct of the Zika virus NS2B-NS3 protease","volume":"142","author":"MC Mahawaththa","year":"2017","journal-title":"Antiviral Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.bbagen.2008.03.018","article-title":"A comparative biochemical analysis of the NS2B (H)\u2013NS3pro protease complex from four dengue virus serotypes","volume":"1780","author":"T Iempridee","year":"2008","journal-title":"Biochim Biophys Acta- Gen Subj"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"28766","DOI":"10.1074\/jbc.M500588200","article-title":"Functional profiling of recombinant NS3 proteases from all four serotypes of dengue virus using tetrapeptide and octapeptide substrate libraries","volume":"280","author":"J Li","year":"2005","journal-title":"J Biol Chem"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nsmb1073","article-title":"Structural basis for the activation of flaviviral NS3 proteases from dengue and West Nile virus","volume":"13","author":"P Erbel","year":"2006","journal-title":"Nat Struct Mol Biol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.antiviral.2012.09.007","article-title":"Structural biology of dengue virus enzymes: towards rational design of therapeutics","volume":"96","author":"CG Noble","year":"2012","journal-title":"Antiviral Res"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.antiviral.2015.03.014","article-title":"The flavivirus NS2B\u2013NS3 protease\u2013helicase as a target for antiviral drug development","volume":"118","author":"D Luo","year":"2015","journal-title":"Antivir Res"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"12891","DOI":"10.1074\/jbc.M112.442723","article-title":"NMR analysis of a novel enzymatically active unlinked dengue NS2B-NS3 protease complex","volume":"288","author":"YM Kim","year":"2013","journal-title":"J Bio Chem"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1016\/j.febslet.2014.05.018","article-title":"The dengue virus NS2B\u2013NS3 protease retains the closed conformation in the complex with BPTI","volume":"588","author":"W-N Chen","year":"2014","journal-title":"FEBS Lett"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.bmc.2014.12.015","article-title":"Flavonoids as noncompetitive inhibitors of Dengue virus NS2B-NS3 protease: Inhibition kinetics and docking studies","volume":"23","author":"LRF de Sousa","year":"2015","journal-title":"Bioorg Medic Chem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.antiviral.2017.02.002","article-title":"Novel antiviral activity and mechanism of bromocriptine as a Zika virus NS2B-NS3 protease inhibitor","volume":"141","author":"JF-W Chan","year":"2017","journal-title":"Antivir Res"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1126\/science.aag2419","article-title":"Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor","volume":"353","author":"J Lei","year":"2016","journal-title":"Science"},{"key":"ref35","article-title":"Identification of novel small molecule inhibitors against NS2B\/NS3 serine protease from Zika virus","author":"H Lee","year":"2016","journal-title":"Antivir Res"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/5815","article-title":"A gradual disruption of tight side\u2013chain packing: 2D 1 H\u2013NMR characterization of acid\u2013induced unfolding of CHABII","volume":"6","author":"J Song","year":"1999","journal-title":"Nat Struct Biol"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"e1002338","DOI":"10.1371\/journal.pbio.1002338","article-title":"ALS-causing mutations significantly perturb the self-assembly and interaction with nucleic acid of the intrinsically disordered prion-like domain of TDP-43","volume":"14","author":"L Lim","year":"2016","journal-title":"PLoS Biol"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"3607","DOI":"10.1021\/cr030403s","article-title":"Unfolded proteins and protein folding studied by NMR","volume":"104","author":"HJ Dyson","year":"2004","journal-title":"Chem Rev"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2795","DOI":"10.1110\/ps.062465306","article-title":"Sensitivity of secondary structure propensities to sequence differences between \u03b1-and \u03b3-synuclein: Implications for fibrillation","volume":"15","author":"JA Marsh","year":"2006","journal-title":"Protein Sci"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1128\/JVI.06225-11","article-title":"Ligand-bound structures of the dengue virus protease reveal the active conformation","volume":"86","author":"CG Noble","year":"2012","journal-title":"J Virol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1074\/jbc.M109.064824","article-title":"Structural characterization of the EphA4-Ephrin-B2 complex reveals new features enabling Eph-ephrin binding promiscuity","volume":"285","author":"H Qin","year":"2010","journal-title":"J Biol Chem"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"19205","DOI":"10.1074\/jbc.M500330200","article-title":"Structural insight into the binding diversity between the Tyr-phosphorylated human ephrinBs and Nck2 SH2 domain","volume":"280","author":"X Ran","year":"2005","journal-title":"J Biol Chem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/cr.2016.116","article-title":"Mechanisms of activation and inhibition of Zika virus NS2B-NS3 protease","volume":"26","author":"X Chen","year":"2016","journal-title":"Cell Res"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"6589","DOI":"10.1021\/cr400525m","article-title":"Classification of intrinsically disordered regions and proteins","volume":"114","author":"R Van Der Lee","year":"2014","journal-title":"Chem Rev"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e39261","DOI":"10.1371\/journal.pone.0039261","article-title":"Intrinsically unstructured domain 3 of hepatitis C Virus NS5A forms a \u201cfuzzy complex\u201d with VAPB-MSP domain which carries ALS-causing mutations","volume":"7","author":"G Gupta","year":"2012","journal-title":"PLoS One"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1039\/C4MB00027G","article-title":"The intrinsic disorder status of the human hepatitis C virus proteome","volume":"10","author":"X Fan","year":"2014","journal-title":"Mol BioSys"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility","volume":"30","author":"GM Morris","year":"2009","journal-title":"J Comput Chem"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1021\/ci700388k","article-title":"Docking of noncompetitive inhibitors into dengue virus type 2 protease: understanding the interactions with allosteric binding sites","volume":"48","author":"R Othman","year":"2008","journal-title":"J Chem Info Modell"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1139\/o98-046","article-title":"NMR for the design of functional mimetics of protein-protein interactions: one key is in the building of bridges","volume":"76","author":"J Song","year":"1998","journal-title":"Biochem Cell Biol"},{"key":"ref50","first-page":"123","article-title":"Dynamics in Enzyme Catalysis","author":"B Ma","year":"2013"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1038\/nchembio.2212","article-title":"Protein dynamics: Conformational footprints","volume":"12","author":"B Ma","year":"2016","journal-title":"Nat Chem Biol"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"6391","DOI":"10.1021\/acs.chemrev.5b00623","article-title":"The role of protein loops and linkers in conformational dynamics and allostery","volume":"116","author":"E Papaleo","year":"2016","journal-title":"Chem Rev"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"2744","DOI":"10.1021\/cb400612h","article-title":"Allosteric inhibition of the NS2B-NS3 protease from dengue virus","volume":"8","author":"M Yildiz","year":"2013","journal-title":"ACS Chem Biol"},{"issue":"3","key":"ref54","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1007\/s10529-016-2261-6","article-title":"Inhibitory effect of flavonoids against NS2B-NS3 protease of ZIKA virus and their structure activity relationship","volume":"39","author":"HJ Lim","year":"2017","journal-title":"Biotechnol Lett"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1080\/10715769900301351","article-title":"Health effects and bioavailability of dietary flavonols","volume":"31","author":"PC Hollman","year":"1999","journal-title":"Free Radic Res"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"e0128132","DOI":"10.1371\/journal.pone.0128132","article-title":"Flavonoid intake in European adults (18 to 64 years)","volume":"10","author":"A Vogiatzoglou","year":"2015","journal-title":"PloS One"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1476-4598-10-12","article-title":"Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma","volume":"10","author":"R Wilken","year":"2011","journal-title":"Mol Cancer"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1021\/cb500413n","article-title":"Dynamic principle for designing antagonistic\/agonistic molecules for EphA4 receptor, the only known ALS modifier","volume":"10","author":"H Qin","year":"2014","journal-title":"ACS Chem Biol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"e1001084","DOI":"10.1371\/journal.pcbi.1001084","article-title":"Dynamically-driven inactivation of the catalytic machinery of the SARS 3C-like protease by the N214A mutation on the extra domain","volume":"7","author":"J Shi","year":"2011","journal-title":"PLoS Comput Biol"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"24765","DOI":"10.1074\/jbc.M311744200","article-title":"Dissection Study on the Severe Acute Respiratory Syndrome 3C-like Protease reveals the critical role of the extra domain in dimerization of the enzyme defining the extra domain as a new target for design of highly specific protease inhibitors","volume":"279","author":"J Shi","year":"2004","journal-title":"J Biol Chem"},{"key":"ref61","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780195171792.001.0001","article-title":"Fitting models to biological data using linear and nonlinear regression: a practical guide to curve fitting","author":"H Motulsky","year":"2004"},{"key":"ref62","first-page":"17","article-title":"Avogadro: an advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"MD Hanwell","year":"2012","journal-title":"J Chem Inf"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0180632","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T06:21:59Z","timestamp":1719296519000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0180632"}},"subtitle":[],"editor":[{"given":"Eugene A.","family":"Permyakov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,7,10]]},"references-count":62,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7,10]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0180632","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,10]]}}}