Abstract：
:Ebola virus (EBOV), a negative-sense RNA virus in the family Filoviridae, is known to cause severe hemorrhagic fever in humans and other primates. Infection with EBOV causes a high mortality rate and currently there is no FDA-licensed vaccine or therapeutic treatment available. Recently, heat-shock protein 90 (Hsp90), a molecular chaperone, was shown to be an important host factor for the replication of several negative-strand viruses. We tested the effect of several different Hsp90 inhibitors including geldanamycin, radicicol, and 17-allylamino-17-demethoxygeldanamycin (17-AAG; a geldanamycin analog) on the replication of Zaire EBOV. Our results showed that inhibition of Hsp90 significantly reduced the replication of EBOV. Classic Hsp90 inhibitors reduced viral replication with an effective concentration at 50% (EC(50)) in the high nanomolar to low micromolar range, while drugs from a new class of Hsp90 inhibitors showed markedly more potent inhibition. These compounds blocked EBOV replication with an EC(50) in the low nanomolar range and showed significant potency in blocking replication in primary human monocytes. These results validated that Hsp90 is an important host factor for the replication of filoviruses and suggest that Hsp90 inhibitors may be therapeutically effective in treating EBOV infection.
journal_name
Antiviral Resjournal_title
Antiviral researchauthors
Smith DR,McCarthy S,Chrovian A,Olinger G,Stossel A,Geisbert TW,Hensley LE,Connor JHdoi
10.1016/j.antiviral.2010.04.015subject
Has Abstractpub_date
2010-08-01 00:00:00pages
187-94issue
2eissn
0166-3542issn
1872-9096pii
S0166-3542(10)00604-2journal_volume
87pub_type
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更新日期：2010-12-01 00:00:00
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更新日期：2000-01-01 00:00:00
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更新日期：2006-09-01 00:00:00
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更新日期：2020-05-01 00:00:00
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更新日期：2020-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：2016-06-01 00:00:00
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