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Viruses 2018, 10(6), 301; https://doi.org/10.3390/v10060301

Inhibition of Hepatitis E Virus Spread by the Natural Compound Silvestrol

1
Department of Virology, Paul-Ehrlich-Institut, 63225 Langen, Germany
2
Federal Institute for Risk Assessment, 10589 Berlin, Germany
3
Department of Allergology, Paul-Ehrlich-Institut, 63225 Langen, Germany
4
Institute of Pharmaceutical Chemistry, Philipps-Universität Marburg, 35037 Marburg, Germany
5
German Center for Infection Research (DZIF), 38124 Braunschweig, Germany
*
Author to whom correspondence should be addressed.
Received: 19 April 2018 / Revised: 18 May 2018 / Accepted: 31 May 2018 / Published: 2 June 2018
(This article belongs to the Section Antivirals & Vaccines)
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Abstract

Every year, there are about 20 Mio hepatitis E virus (HEV) infections and 60,000 deaths that are associated with HEV worldwide. At the present, there exists no specific therapy for HEV. The natural compound silvestrol has a potent antiviral effect against the (−)-strand RNA-virus Ebola virus, and also against the (+)-strand RNA viruses Corona-, Picorna-, and Zika virus. The inhibitory effect on virus spread is due to an inhibition of the DEAD-box RNA helicase eIF4A, which is required to unwind structured 5′-untranslated regions (UTRs). This leads to an impaired translation of viral RNA. The HEV (+)-strand RNA genome contains a 5′-capped, short 5′-UTR. This study aims to analyze the impact of silvestrol on the HEV life cycle. Persistently infected A549 cells were instrumental. This study identifies silvestrol as a potent inhibitor of the release of HEV infectious viral particles. This goes along with a strongly reduced HEV capsid protein translation, retention of viral RNA inside the cytoplasm, and without major cytotoxic effects. Interestingly, in parallel silvestrol affects the activity of the antiviral major vault protein (MVP) by translocation from the cytoplasm to the perinuclear membrane. These data further characterize the complex antiviral activity of silvestrol and show silvestrol’s broad spectrum of function, since HEV is a virus without complex secondary structures in its genome, but it is still affected. View Full-Text
Keywords: HEV; silvestrol; antiviral; eIF4A; MVP HEV; silvestrol; antiviral; eIF4A; MVP
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Glitscher, M.; Himmelsbach, K.; Woytinek, K.; Johne, R.; Reuter, A.; Spiric, J.; Schwaben, L.; Grünweller, A.; Hildt, E. Inhibition of Hepatitis E Virus Spread by the Natural Compound Silvestrol. Viruses 2018, 10, 301.

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