Assessment of the potential for host-targeted iminosugars UV-4 and UV-5 activity against filovirus infections in vitro and in vivo

详细信息    查看全文

• 作者：Kelly L. Warfield^a ; ^{warfieldk@ebsi.com} ; Travis K. Warren^b ; ^{travis.k.warren.ctr@mail.mil} ; Xiangguo Qiu^c ; ^{Xiangguo.qiu@phac-aspc.gc.ca} ; Jay Wells^b ; ^{jay.b.wells.ctr@mail.mil} ; Chad E. Mire^d ; ^{cmire@utmb.edu} ; Joan B. Geisbert^d ; ^{jbgeisbe@utmb.edu} ; Kelly S. Stuthman^b ; ^{Kelly.s.stuthman.ctr@mail.mil} ; Nicole L. Garza^b ; ^{nicole.l.lackemeyer.ctr@mail.mil} ; Sean A. Van Tongeren^b ; ^{sean.a.vantongeren.ctr@mail.mil} ; Amy C. Shurtleff^b ; ^{amy.c.shurtleff.ctr@mail.mil} ; Krystle N. Agans^d ; ^{knagans@utmb.edu} ; Gary Wong^c ; ^e ; ^{garyckwong@hotmail.com} ; Michael V. Callahan^f ; ^g ; ^{mvcallahan@mgh.harvard.edu} ; Thomas W. Geisbert^d ; ^{twgeisbe@utmb.edu} ; Brennan Klose^f ; ^{brennan.klose@abviro.com} ; Urban Ramstedt^f ; ^{urban_ramstedt@yahoo.com} ; Anthony M. Treston^a ; ^{trestona@ebsi.com}
• 关键词：Iminosugar ; UV-4B ; Ebola virus ; Marburg virus ; Antiviral ; Glucosidase
• 刊名：Antiviral Research
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：138
• 期：Complete
• 页码：22-31
• 全文大小：1400 K
• 卷排序：138

文摘

Iminosugars are host-directed antivirals that inhibit glycosylation pathways. Iminosugar analogs based on NB-DNJ demonstrated in vitro activity against live EBOV and MARV. In vivo efficacy studies provided inconsistent data following treatment with iminosugars using filovirus mouse models. UV-4B did not provide clinical benefit in a small proof-of-concept macaque efficacy trial when dosed once per day.