A screen of approved drugs and molecular probes identifies therapeutics with anti-Ebola virus activity

被引：180

作者：

Johansen, Lisa M. ^{[1
]}

DeWald, Lisa Evans ^{[2
]}

Shoemaker, Charles J. ^{[3
]}

Hoffstrom, Benjamin G. ^{[1
]}

Lear-Rooney, Calli M. ^{[2
]}

Stossel, Andrea ^{[2
]}

Nelson, Elizabeth ^{[3
]}

Delos, Sue E. ^{[3
]}

Simmons, James A. ^{[3
]}

Grenier, Jill M. ^{[1
]}

Pierce, Laura T. ^{[1
]}

Pajouhesh, Hassan ^{[1
]}

Lehar, Joseph ^{[1
,4
]}

Hensley, Lisa E. ^{[2
]}

Glass, Pamela J. ^{[2
]}

White, Judith M. ^{[3
]}

Olinger, Gene G. ^{[2
]}

机构：

[1] Horizon Discovery Inc, Cambridge, MA 02142 USA

[2] US Army Med Res Inst Infect Dis, Frederick, MD 21702 USA

[3] Univ Virginia, Charlottesville, VA 22908 USA

[4] Boston Univ, Bioinformat Program, Boston, MA 02215 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2015年 / 7卷 / 290期

关键词：

ENTRY REQUIRES; MOUSE MODEL; CELL ENTRY; GLYCOPROTEIN; INHIBITORS; BINDING; FUSION; ACID; PATHOGENESIS; REPLICATION;

D O I：

10.1126/scitranslmed.aaa5597

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Currently, no approved therapeutics exist to treat or prevent infections induced by Ebola viruses, and recent events have demonstrated an urgent need for rapid discovery of new treatments. Repurposing approved drugs for emerging infections remains a critical resource for potential antiviral therapies. We tested similar to 2600 approved drugs and molecular probes in an in vitro infection assay using the type species, Zaire ebolavirus. Selective antiviral activity was found for 80 U.S. Food and Drug Administration-approved drugs spanning multiple mechanistic classes, including selective estrogen receptor modulators, antihistamines, calcium channel blockers, and antidepressants. Results using an in vivo murine Ebola virus infection model confirmed the protective ability of several drugs, such as bepridil and sertraline. Viral entry assays indicated that most of these antiviral drugs block a late stage of viral entry. By nature of their approved status, these drugs have the potential to be rapidly advanced to clinical settings and used as therapeutic countermeasures for Ebola virus infections.

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页数：13

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