Inhibition of heat-shock protein 90 reduces Ebola virus replication

Darci R. Smith, Sarah McCarthy, Andrew Chrovian, Gene Olinger, Andrea Stossel, Thomas Geisbert, Lisa E. Hensley, John H. Connor

Research output: Contribution to journalArticle

70 Scopus citations

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% (EC50) 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 EC50 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.

Original languageEnglish (US)
Pages (from-to)187-194
Number of pages8
JournalAntiviral Research
Volume87
Issue number2
DOIs
StatePublished - Aug 2010
Externally publishedYes

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Keywords

  • Ebola virus
  • Hsp90
  • Therapeutic

ASJC Scopus subject areas

  • Virology
  • Pharmacology
  • Medicine(all)

Cite this

Smith, D. R., McCarthy, S., Chrovian, A., Olinger, G., Stossel, A., Geisbert, T., Hensley, L. E., & Connor, J. H. (2010). Inhibition of heat-shock protein 90 reduces Ebola virus replication. Antiviral Research, 87(2), 187-194. https://doi.org/10.1016/j.antiviral.2010.04.015