{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T09:10:09Z","timestamp":1790500209900,"version":"4.1.0"},"reference-count":51,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005892","name":"China Academy of Chinese Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005892","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2020,7]]},"DOI":"10.1016\/j.bcp.2020.113962","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T19:43:41Z","timestamp":1586202221000},"page":"113962","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":60,"special_numbering":"C","title":["Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection"],"prefix":"10.1016","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7936-1727","authenticated-orcid":false,"given":"Min","family":"Zou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1950-6576","authenticated-orcid":false,"given":"Xingang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changwen","family":"Ke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"5","key":"10.1016\/j.bcp.2020.113962_b0005","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":"Dick","year":"1952","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"issue":"24","key":"10.1016\/j.bcp.2020.113962_b0010","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika Virus Outbreak on Yap Island, Federated States of Micronesia","volume":"360","author":"Duffy","year":"2009","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"10.1016\/j.bcp.2020.113962_b0015","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.3201\/eid2006.140138","article-title":"Zika Virus, French Polynesia, South Pacific, 2013","volume":"20","author":"Cao-Lormeau","year":"2014","journal-title":"Emerg. Infect. Dis."},{"key":"10.1016\/j.bcp.2020.113962_b0020","unstructured":"World Health Organization Zika virus situation report \u2013 5th February 2016 Available online: http:\/\/www.who.int\/emergencies\/zika-virus\/situation-report\/5- february-2016\/en\/. (accessed on 30 June 2019)."},{"key":"10.1016\/j.bcp.2020.113962_b0025","unstructured":"World Health Organization. 2019. Zika epidemiology update."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0030","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002203","article-title":"Zika virus infection as a cause of congenital brain abnormalities and guillain-barre syndrome: systematic review","volume":"14","author":"Krauer","year":"2017","journal-title":"PLoS Med."},{"issue":"16","key":"10.1016\/j.bcp.2020.113962_b0035","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1056\/NEJMc1602964","article-title":"Zika virus associated with meningoencephalitis","volume":"374","author":"Carteaux","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"10026","key":"10.1016\/j.bcp.2020.113962_b0040","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/S0140-6736(16)00644-9","article-title":"Acute myelitis due to Zika virus infection","volume":"387","author":"Mecharles","year":"2016","journal-title":"Lancet"},{"issue":"24","key":"10.1016\/j.bcp.2020.113962_b0045","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.1056\/NEJMoa1602412","article-title":"Zika virus infection in pregnant women in Rio de Janeiro","volume":"375","author":"Brasil","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"10","key":"10.1016\/j.bcp.2020.113962_b0050","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1056\/NEJMoa1600651","article-title":"Zika Virus associated with microcephaly","volume":"374","author":"Mlakar","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"16","key":"10.1016\/j.bcp.2020.113962_b0055","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1056\/NEJMp1602708","article-title":"Zika Virus as a Cause of Neurologic Disorders","volume":"374","author":"Broutet","year":"2016","journal-title":"N. Engl. J. Med."},{"issue":"6","key":"10.1016\/j.bcp.2020.113962_b0060","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/14787210.2018.1483239","article-title":"Zika virus, vaccines, and antiviral strategies","volume":"16","author":"Masmejan","year":"2018","journal-title":"Expert Rev. Anti-Infect. Ther."},{"issue":"2","key":"10.1016\/j.bcp.2020.113962_b0065","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.celrep.2016.12.045","article-title":"Axl mediates ZIKA virus entry in human glial cells and modulates innate immune responses","volume":"18","author":"Meertens","year":"2017","journal-title":"Cell Rep."},{"issue":"4","key":"10.1016\/j.bcp.2020.113962_b0070","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s11684-017-0589-5","article-title":"Development of small-molecule viral inhibitors targeting various stages of the life cycle of emerging and re-emerging viruses","volume":"11","author":"Wang","year":"2017","journal-title":"Front. Med-Pro."},{"issue":"4","key":"10.1016\/j.bcp.2020.113962_b0075","doi-asserted-by":"crossref","first-page":"S75","DOI":"10.1074\/mcp.R116.065649","article-title":"Protein Interactions during the Flavivirus and Hepacivirus Life Cycle","volume":"16","author":"Gerold","year":"2017","journal-title":"Mol. Cell. Proteomics"},{"key":"10.1016\/j.bcp.2020.113962_b0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/1734151","article-title":"New Targets for Zika Virus Determined by Human-Viral Interactomic: A Bioinformatics Approach","volume":"2017","author":"Esteves","year":"2017","journal-title":"Biomed Res. Int."},{"issue":"21","key":"10.1016\/j.bcp.2020.113962_b0085","doi-asserted-by":"crossref","first-page":"11815","DOI":"10.1128\/JVI.01022-12","article-title":"Flavivirus Replication Complex Assembly Revealed by DNAJC14 Functional Mapping","volume":"86","author":"Yi","year":"2012","journal-title":"J. Virol."},{"key":"10.1016\/j.bcp.2020.113962_b0090","doi-asserted-by":"crossref","first-page":"14762","DOI":"10.1038\/ncomms14762","article-title":"Structure and function of the Zika virus full-length NS5 protein","volume":"8","author":"Zhao","year":"2017","journal-title":"Nat. Commun."},{"issue":"2","key":"10.1016\/j.bcp.2020.113962_b0095","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s11481-017-9736-7","article-title":"Host-Virus Interaction of ZIKA Virus in Modulating Disease Pathogenesis","volume":"12","author":"Routhu","year":"2017","journal-title":"J. Neuroimmune Pharm."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0100","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1038\/nrmicro1067","article-title":"A structural perspective of the Flavivirus life cycle","volume":"3","author":"Mukhopadhyay","year":"2005","journal-title":"Nat. Rev. Microbiol."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0105","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1006\/viro.2002.1635","article-title":"Sequence diversity of the capsid gene and the nonstructural gene NS2B of dengue-3 virus in vivo","volume":"303","author":"Wang","year":"2002","journal-title":"Virology"},{"key":"10.1016\/j.bcp.2020.113962_b0110","series-title":"Fields Virology","first-page":"747","author":"Pierson","year":"2013"},{"issue":"16","key":"10.1016\/j.bcp.2020.113962_b0115","doi-asserted-by":"crossref","first-page":"10376","DOI":"10.1128\/JVI.79.16.10376-10385.2005","article-title":"Early alpha\/beta interferon production by myeloid dendritic cells in response to UV-inactivated virus requires viral entry and interferon regulatory factor 3 but not MyD88","volume":"79","author":"Hidmark","year":"2005","journal-title":"J. Virol."},{"issue":"10","key":"10.1016\/j.bcp.2020.113962_b0120","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1002934","article-title":"DENV inhibits type I IFN production in infected cells by cleaving human STING","volume":"8","author":"Aguirre","year":"2012","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.bcp.2020.113962_b0125","first-page":"49","article-title":"Identification of novel small molecule inhibitors against NS2B\/NS3 serine protease from Zika virus","volume":"254","author":"Lee","year":"2017","journal-title":"Abstr. Pap. Am. Chem. S."},{"key":"10.1016\/j.bcp.2020.113962_b0130","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.antiviral.2016.03.010","article-title":"Zika virus: History, emergence, biology, and prospects for control","volume":"130","author":"Weaver","year":"2016","journal-title":"Antivir. Res."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0135","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-018-38450-1","article-title":"Computational screening of medicinal plant phytochemicals to discover potent pan-serotype inhibitors against dengue virus","volume":"9","author":"Tahir ul Qamar","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bcp.2020.113962_b0140","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.ijbiomac.2017.06.105","article-title":"Epigallocatechin gallate, an active green tea compound inhibits the Zika virus entry into host cells via binding the envelope protein","volume":"104","author":"Sharma","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"10.1016\/j.bcp.2020.113962_b0145","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.antiviral.2017.03.014","article-title":"Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding","volume":"142","author":"Mounce","year":"2017","journal-title":"Antivir. Res."},{"issue":"4","key":"10.1016\/j.bcp.2020.113962_b0150","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.3390\/ijms19041093","article-title":"The Flavonoid Isoquercitrin Precludes Initiation of Zika Virus Infection in Human Cells","volume":"19","author":"Gaudry","year":"2018","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"10.1016\/j.bcp.2020.113962_b0155","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1007\/s00705-018-4083-4","article-title":"Baicalein and baicalin as Zika virus inhibitors","volume":"164","author":"Oo","year":"2019","journal-title":"Arch. Virol."},{"key":"10.1016\/j.bcp.2020.113962_b0160","doi-asserted-by":"crossref","first-page":"16348","DOI":"10.1038\/s41598-019-52626-3","article-title":"The citrus flavonoid naringenin impairs the in vitro infection of human cells by Zika virus","volume":"9","author":"Cataneo","year":"2019","journal-title":"Sci. Rep-UK"},{"key":"10.1016\/j.bcp.2020.113962_b0165","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.antiviral.2019.04.003","article-title":"Antiviral activity of pinocembrin against Zika virus replication","volume":"167","author":"Lee","year":"2019","journal-title":"Antivir. Res."},{"issue":"3","key":"10.1016\/j.bcp.2020.113962_b0170","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":"Lim","year":"2017","journal-title":"Biotechnol. Lett."},{"issue":"7","key":"10.1016\/j.bcp.2020.113962_b0175","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180632","article-title":"Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants","volume":"12","author":"Roy","year":"2017","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0180","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s12900-018-0084-5","article-title":"Structure activity relationship (SAR) and quantitative structure activity relationship (QSAR) studies showed plant flavonoids as potential inhibitors of dengue NS2B-NS3 protease","volume":"18","author":"Sarwar","year":"2018","journal-title":"BMC Struct. Biol."},{"key":"10.1016\/j.bcp.2020.113962_b0185","article-title":"Investigating into the molecular interactions of flavonoids targeting NS2B-NS3 protease from ZIKA virus through in-silico approaches","author":"Yadav","year":"2020","journal-title":"J. Biomol. Struct. Dyn."},{"issue":"3","key":"10.1016\/j.bcp.2020.113962_b0190","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":"de Sousa","year":"2015","journal-title":"Bioorgan. Med. Chem."},{"issue":"7","key":"10.1016\/j.bcp.2020.113962_b0195","doi-asserted-by":"crossref","first-page":"165","DOI":"10.3390\/v9070165","article-title":"Effective Suckling C57BL\/6, Kunming, and BALB\/c Mouse Models with Remarkable Neurological Manifestation for Zika Virus Infection","volume":"9","author":"Yu","year":"2017","journal-title":"Viruses-Basel"},{"issue":"7","key":"10.1016\/j.bcp.2020.113962_b0200","doi-asserted-by":"crossref","first-page":"591","DOI":"10.3390\/v11070591","article-title":"Storage-Dependent Generation of Potent Anti-ZIKV Activity in Human Breast Milk","volume":"11","author":"Conzelmann","year":"2019","journal-title":"Viruses-Basel"},{"issue":"11","key":"10.1016\/j.bcp.2020.113962_b0205","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":"Chen","year":"2016","journal-title":"Cell Res."},{"issue":"9","key":"10.1016\/j.bcp.2020.113962_b0210","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.1517\/13543784.9.9.2103","article-title":"The therapeutic potential of flavonoids","volume":"9","author":"Wang","year":"2000","journal-title":"Expert Opin. Invest. Drugs"},{"key":"10.1016\/j.bcp.2020.113962_b0215","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.antiviral.2017.12.003","article-title":"A flavonoid compound library screen revealed potent antiviral activity of plant-derived flavonoids on human enterovirus A71 replication","volume":"150","author":"Min","year":"2018","journal-title":"Antivir. Res."},{"issue":"3","key":"10.1016\/j.bcp.2020.113962_b0220","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1002\/hep.24803","article-title":"(-)-Epigallocatechin-3-gallate is a new inhibitor of hepatitis C virus entry","volume":"55","author":"Calland","year":"2012","journal-title":"Hepatology"},{"issue":"5","key":"10.1016\/j.bcp.2020.113962_b0225","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1111\/bph.12009","article-title":"Anti-infective properties of epigallocatechin-3-gallate (EGCG), a component of green tea","volume":"168","author":"Steinmann","year":"2013","journal-title":"Brit. J. Pharmacol."},{"key":"10.1016\/j.bcp.2020.113962_b0230","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.virol.2016.06.012","article-title":"The green tea molecule EGCG inhibits Zika virus entry","volume":"496","author":"Carneiro","year":"2016","journal-title":"Virology"},{"key":"10.1016\/j.bcp.2020.113962_b0235","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.antiviral.2017.04.016","article-title":"Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles","volume":"143","author":"Albulescu","year":"2017","journal-title":"Antivir. Res."},{"key":"10.1016\/j.bcp.2020.113962_b0240","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.antiviral.2017.04.017","article-title":"Polysulfonate suramin inhibits Zika virus infection","volume":"143","author":"Tan","year":"2017","journal-title":"Antivir. Res."},{"key":"10.1016\/j.bcp.2020.113962_b0245","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.antiviral.2018.10.019","article-title":"Zika virus NS2B\/NS3 proteinase: A new target for an old drug - Suramin a lead compound for NS2B\/NS3 proteinase inhibition","volume":"160","author":"Coronado","year":"2018","journal-title":"Antivir. Res."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0250","first-page":"12","article-title":"Bioactive flavonoids in medicinal plants: Structure, activity and biological fate","volume":"13","author":"Wang","year":"2018","journal-title":"Asian J. Pharm. Sci."},{"issue":"1","key":"10.1016\/j.bcp.2020.113962_b0255","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.enzmictec.2012.10.001","article-title":"The influence of flavonoid compounds on the in vitro inhibition study of a human fibroblast collagenase catalytic domain expressed in E. coli","volume":"52","author":"Thi","year":"2013","journal-title":"Enzyme Microb. Tech."}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295220301908?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295220301908?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T13:16:52Z","timestamp":1757769412000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295220301908"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7]]},"references-count":51,"alternative-id":["S0006295220301908"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2020.113962","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2020,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Structure-activity relationship of flavonoid bifunctional inhibitors against Zika virus infection","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2020.113962","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"113962"}}