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Ultrastructural Analysis of Chikungunya Virus Dissemination from the Midgut of the Yellow Fever Mosquito, Aedes aegypti
Open AccessArticle

Silvestrol Inhibits Chikungunya Virus Replication

1
Paul-Ehrlich-Institut, Department of Virology, 63225 Langen, Germany
2
Institut für Pharmazeutische Chemie, Philipps-Universität Marburg, 35032 Marburg, Germany
*
Author to whom correspondence should be addressed.
Viruses 2018, 10(11), 592; https://doi.org/10.3390/v10110592
Received: 11 September 2018 / Revised: 19 October 2018 / Accepted: 26 October 2018 / Published: 30 October 2018
(This article belongs to the Special Issue Chikungunya Virus and (Re-) Emerging Alphaviruses)
Silvestrol, a natural compound that is isolated from plants of the genus Aglaia, is a specific inhibitor of the RNA helicase eIF4A, which unwinds RNA secondary structures in 5′-untranslated regions (UTRs) of mRNAs and allows translation. Silvestrol has a broad antiviral activity against multiple RNA virus families. Here, we show that silvestrol inhibits the replication of chikungunya virus (CHIKV), a positive single-stranded RNA virus. Silvestrol delayed the protein synthesis of non-structural (nsPs) and structural proteins, resulting in a delayed innate response to CHIKV infection. Interferon-α induced STAT1 phosphorylation was not inhibited nor did eIF2α become phosphorylated 16 h post infection in the presence of silvestrol. In addition, the host protein shut-off induced by CHIKV infection was decreased in silvestrol-treated cells. Silvestrol acts by limiting the amount of nsPs, and thereby reducing CHIKV RNA replication. From our results, we propose that inhibition of the host helicase eIF4A might have potential as a therapeutic strategy to treat CHIKV infections. View Full-Text
Keywords: chikungunya virus; silvestrol; translation; eIF4A; antiviral chikungunya virus; silvestrol; translation; eIF4A; antiviral
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MDPI and ACS Style

Henss, L.; Scholz, T.; Grünweller, A.; Schnierle, B.S. Silvestrol Inhibits Chikungunya Virus Replication. Viruses 2018, 10, 592.

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