{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T19:40:41Z","timestamp":1786995641728,"version":"build-2736575974"},"reference-count":31,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100019018","name":"Chinese Academy of Medical Sciences Initiative for Innovative Medicine","doi-asserted-by":"publisher","award":["2021-I2M-1-038"],"award-info":[{"award-number":["2021-I2M-1-038"]}],"id":[{"id":"10.13039\/501100019018","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174087"],"award-info":[{"award-number":["82174087"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Phytomedicine"],"published-print":{"date-parts":[[2025,10]]},"DOI":"10.1016\/j.phymed.2025.157105","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T13:46:33Z","timestamp":1754401593000},"page":"157105","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Neferine inhibits Zika virus replication by targeting viral protease"],"prefix":"10.1016","volume":"146","author":[{"given":"Senfeng","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingting","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongrong","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3358-0411","authenticated-orcid":false,"given":"Shan","family":"Cen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizhong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.phymed.2025.157105_bib0001","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1021\/acs.jmedchem.9b00775","article-title":"Drugs for the treatment of Zika virus infection","volume":"63","author":"Bernatchez","year":"2020","journal-title":"J. Med. Chem"},{"issue":"7","key":"10.1016\/j.phymed.2025.157105_bib0002","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.14336\/AD.2021.0318","article-title":"Targeting NLRP3 inflammasome in the treatment of diabetes and diabetic complications: role of natural compounds from herbal medicine","volume":"12","author":"Bai","year":"2021","journal-title":"Aging Dis"},{"issue":"3","key":"10.1016\/j.phymed.2025.157105_bib0003","article-title":"The role of natural products in modern drug discovery","volume":"91","author":"Calixto","year":"2019","journal-title":"An. Acad. Bras Cienc"},{"issue":"4","key":"10.1016\/j.phymed.2025.157105_bib0004","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1093\/ofid\/ofw175","article-title":"Adenosine analog NITD008 is a potent inhibitor of Zika virus","volume":"3","author":"Deng","year":"2016","journal-title":"Open Forum. Infect. Dis"},{"issue":"10","key":"10.1016\/j.phymed.2025.157105_bib0005","doi-asserted-by":"crossref","first-page":"1190","DOI":"10.1001\/jamaneurol.2017.1703","article-title":"Neurologic complications associated with the Zika virus in Brazilian adults","volume":"74","author":"Da Silva","year":"2017","journal-title":"JAMA Neurol"},{"issue":"1","key":"10.1016\/j.phymed.2025.157105_bib0006","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1038\/s41467-018-04776-7","article-title":"The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity","volume":"9","author":"Do\u00f1ate-Maci\u00e1n","year":"2018","journal-title":"Nat. Commun"},{"issue":"18","key":"10.1016\/j.phymed.2025.157105_bib0008","doi-asserted-by":"crossref","first-page":"3963","DOI":"10.1016\/j.bmc.2019.07.038","article-title":"Peptide derivatives as inhibitors of NS2B-NS3 protease from Dengue, West Nile, and Zika flaviviruses","volume":"27","author":"da Silva-J\u00fanior","year":"2019","journal-title":"Bioorg. Med. Chem."},{"issue":"6283","key":"10.1016\/j.phymed.2025.157105_bib0009","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1126\/science.aaf5036","article-title":"Zika virus in the Americas: early epidemiological and genetic findings","volume":"352","author":"Faria","year":"2016","journal-title":"Science"},{"issue":"8","key":"10.1016\/j.phymed.2025.157105_bib0010","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.micinf.2019.04.005","article-title":"Zika virus infection: an update","volume":"21","author":"Ferraris","year":"2019","journal-title":"Microbes Infect"},{"key":"10.1016\/j.phymed.2025.157105_bib0011","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2024.1418516","article-title":"Recent advances in the study of zika virus structure, drug targets, and inhibitors","volume":"15","author":"Feng","year":"2024","journal-title":"Front. Pharmacol"},{"issue":"1","key":"10.1016\/j.phymed.2025.157105_bib0013","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12915-022-01344-w","article-title":"A gossypol derivative effectively protects against Zika and dengue virus infection without toxicity","volume":"20","author":"Gao","year":"2022","journal-title":"BMC Biol"},{"key":"10.1016\/j.phymed.2025.157105_bib0014","doi-asserted-by":"crossref","DOI":"10.1016\/j.compbiolchem.2023.107876","article-title":"Exploring allosteric hits of the NS2B-NS3 protease of DENV2 by structure-guided screening","volume":"104","author":"Gangopadhyay","year":"2023","journal-title":"Comput. Biol. Chem"},{"issue":"2","key":"10.1016\/j.phymed.2025.157105_bib0015","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.virs.2022.01.007","article-title":"Screening of novel synthetic derivatives of dehydroepiandrosterone for antivirals against flaviviruses infections","volume":"37","author":"Imran","year":"2022","journal-title":"Virol. Sin"},{"key":"10.1016\/j.phymed.2025.157105_bib0016","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1146\/annurev.micro.62.081307.163005","article-title":"Global spread and persistence of dengue","volume":"62","author":"Kyle","year":"2008","journal-title":"Annu. Rev. Microbiol"},{"issue":"2","key":"10.1016\/j.phymed.2025.157105_bib0017","doi-asserted-by":"crossref","first-page":"72","DOI":"10.3390\/v10020072","article-title":"Favipiravir and ribavirin inhibit replication of Asian and African strains of Zika virus in different cell models","volume":"10","author":"Kim","year":"2018","journal-title":"Viruses"},{"issue":"31","key":"10.1016\/j.phymed.2025.157105_bib0018","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":"Li","year":"2005","journal-title":"J. Biol. Chem"},{"issue":"5","key":"10.1016\/j.phymed.2025.157105_bib0019","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.neuron.2016.11.031","article-title":"The neurobiology of Zika virus","volume":"92","author":"Li","year":"2016","journal-title":"Neuron"},{"issue":"3","key":"10.1016\/j.phymed.2025.157105_bib0020","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":"1","key":"10.1016\/j.phymed.2025.157105_bib0021","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.phymed.2025.157105_bib0022","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":"Noble","year":"2012","journal-title":"J. Virol"},{"issue":"22","key":"10.1016\/j.phymed.2025.157105_bib0023","doi-asserted-by":"crossref","first-page":"11348","DOI":"10.1021\/cr500233q","article-title":"Biochemistry and medicinal chemistry of the dengue virus protease","volume":"114","author":"Nitsche","year":"2014","journal-title":"Chem. Rev"},{"issue":"10","key":"10.1016\/j.phymed.2025.157105_bib0024","doi-asserted-by":"crossref","DOI":"10.1128\/genomeA.00121-18","article-title":"Complete genome sequence of a Zika virus strain isolated from the serum of an infected patient in Thailand in 2006","volume":"6","author":"Nitatpattana","year":"2018","journal-title":"Genome. Announc"},{"key":"10.1016\/j.phymed.2025.157105_bib0025","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms13410","article-title":"Structure of the NS2B-NS3 protease from Zika virus after self-cleavage","volume":"7","author":"Phoo","year":"2016","journal-title":"Nat. Commun"},{"issue":"12","key":"10.1016\/j.phymed.2025.157105_bib0026","first-page":"1086","article-title":"Cardiovascular pharmacological effects of bisbenzylisoquinoline alkaloid derivatives","volume":"23","author":"Qian","year":"2002","journal-title":"Acta Pharmacol Sin"},{"key":"10.1016\/j.phymed.2025.157105_bib0027","doi-asserted-by":"crossref","unstructured":"Roy, A., Lim, L., Srivastava, S., Lu, Y., Song, J., 2017. Solution conformations of Zika NS2B-NS3pro and its inhibition by natural products from edible plants. PLoS One. 12 (7), e0180632.","DOI":"10.1371\/journal.pone.0180632"},{"issue":"1","key":"10.1016\/j.phymed.2025.157105_bib0028","doi-asserted-by":"crossref","first-page":"6832","DOI":"10.1038\/s41467-023-42676-7","article-title":"A single amino acid substitution in the capsid protein of Zika virus contributes to a neurovirulent phenotype","volume":"14","author":"Song","year":"2023","journal-title":"Nat. Commun"},{"issue":"12","key":"10.1016\/j.phymed.2025.157105_bib0029","doi-asserted-by":"crossref","first-page":"4656","DOI":"10.1063\/1.1150128","article-title":"High resolution surface plasmon resonance spectroscopy","volume":"70","author":"Tao","year":"1999","journal-title":"Rev. Sci. Instrum."},{"key":"10.1016\/j.phymed.2025.157105_bib0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.coviro.2023.101305","article-title":"Flavivirus nonstructural proteins and replication complexes as antiviral drug targets","volume":"59","author":"van Den Elsen","year":"2023","journal-title":"Curr. Opin. Virol"},{"issue":"1","key":"10.1016\/j.phymed.2025.157105_bib0031","doi-asserted-by":"crossref","first-page":"44","DOI":"10.3390\/v14010044","article-title":"Potential role of flavivirus NS2B-NS3 proteases in viral pathogenesis and anti-flavivirus drug discovery employing animal cells and models: a review","volume":"14","author":"Wahaab","year":"2021","journal-title":"Viruses"},{"issue":"1","key":"10.1016\/j.phymed.2025.157105_bib0032","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41541-024-00889-x","article-title":"Continuing development of vaccines and monoclonal antibodies against Zika virus","volume":"9","author":"Woodson","year":"2024","journal-title":"NPJ Vacc."},{"issue":"3","key":"10.1016\/j.phymed.2025.157105_bib0033","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/s12275-017-7063-6","article-title":"Zika virus: an emerging flavivirus","volume":"55","author":"Yun","year":"2017","journal-title":"J. Microbiol"}],"container-title":["Phytomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325007445?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0944711325007445?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T08:52:23Z","timestamp":1762332743000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0944711325007445"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":31,"alternative-id":["S0944711325007445"],"URL":"https:\/\/doi.org\/10.1016\/j.phymed.2025.157105","relation":{},"ISSN":["0944-7113"],"issn-type":[{"value":"0944-7113","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Neferine inhibits Zika virus replication by targeting viral protease","name":"articletitle","label":"Article Title"},{"value":"Phytomedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.phymed.2025.157105","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier GmbH. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"157105"}}