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Polymeric Prodrugs Targeting Polyamine MetabolismnInhibit Zika Virus Replication 靶向多胺代谢的聚合前体药物抑制寨卡病毒复制

Figshare Pub Date : 2018-08-06 DOI: 10.1021/acs.molpharmaceut.8b00068.s001

NandaKishore Routhu (5596835), Ying Xie (50016), Matthew Dunworth (4424164), Robert A. Casero (1323687), David Oupicky (9355), Siddappa N. Byrareddy (464902)

{"title":"Polymeric Prodrugs Targeting Polyamine MetabolismnInhibit Zika Virus Replication","authors":"NandaKishore Routhu (5596835), Ying Xie (50016), Matthew Dunworth (4424164), Robert A. Casero (1323687), David Oupicky (9355), Siddappa N. Byrareddy (464902)","doi":"10.1021/acs.molpharmaceut.8b00068.s001","DOIUrl":"https://doi.org/10.1021/acs.molpharmaceut.8b00068.s001","url":null,"abstract":"ThenZika virus (ZIKV) is primarily transmitted via an infectednmosquito bite, during sexual intercourse, or in utero mother to childntransmission. When a fetus is infected, both neurological malformationsnand deficits in brain development are frequently manifested. As such,nthere is a need for vaccines or drugs that may be used to cure ZIKVninfections. Metabolic pathways play a crucial role in cell differentiationnand development. More importantly, polyamines play a key role in replicationnand translation of several RNA viruses, including ZIKV, Dengue virus,nand Chikungunya virus. Here, we present polyamine analogues (BENSpmnand PG11047) and their corresponding polymer prodrug derivatives forninhibiting ZIKV infection by intersecting with polyamine catabolismnpathways. We tested the compounds against ZIKV African (MR766) andnAsian (PRVABC59) strains in human kidney epithelial (Vero) and glioblastomanderived (SNB-19) cell lines. Our results demonstrate potent inhibitionnof ZIKV viral replication in both cell lines tested. This antiviralneffect was mediated by the upregulation of two polyamine catabolicnenzymes, spermine oxidase, and spermidine (SMOX)/spermine N1-acetyltransferasen(SAT1) as apparent reduction of the ZIKV infection following heterologousnexpression of SMOX and SAT1. On the basis of these observations, weninfer potential use of these polyamine analogues to treat ZIKV infections.","PeriodicalId":522332,"journal":{"name":"Figshare","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147895422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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