Journalartikel

Jahr der Veröffentlichung: 2018

Seiten: 123-129

Zeitschrift: Antiviral Research

Bandnummer: 150

ISSN: 0166-3542

eISSN: 1872-9096

Open Access Status: Green

DOI Link: https://doi.org/10.1016/j.antiviral.2017.12.010

Verlag: Elsevier

Abstract: 
Coronaviruses (CoV) and picornaviruses are plus-strand RNA viruses that use 5' cap-dependent and cap-independent strategies, respectively, for viral mRNA translation initiation. Here, we analyzed the effects of the plant compound silvestrol, a specific inhibitor of the DEAD-box RNA helicase eIF4A, on viral translation using a dual luciferase assay and virus-infected primary cells. Silvestrol was recently shown to have potent antiviral activity in Ebola virus-infected human macrophages. We found that silvestrol is also a potent inhibitor of cap dependent viral mRNA translation in CoV-infected human embryonic lung fibroblast (MRC-5) cells. EC50 values of 1.3 nM and 3 nM silvestrol were determined for MERS-CoV and HCoV-229E, respectively. For the highly pathogenic MERS-CoV, the potent antiviral activities of silvestrol were also confirmed using peripheral blood mononuclear cells (PBMCs) as a second type of human primary cells. Silvestrol strongly inhibits the expression of CoV structural and nonstructural proteins (N, nsp8) and the formation of viral replication/transcription complexes. Furthermore, potential antiviral effects against human rhinovirus (HRV) Al and poliovirus type 1 (PV), representing different species in the genus Enterovirus (family Picomaviridae), were investigated. The two viruses employ an internal ribosomal entry site (IRES)-mediated translation initiation mechanism. For PV, which is known to require the activity of eIF4A, an EC50 value of 20 nM silvestrol was determined in MRC-5 cells. The higher EC50 value of 100 nM measured for HRV Al indicates a less critical role of eIF4A activity in HRV Al IRES-mediated translation initiation. Taken together, the data reveal a broad-spectrum antiviral activity of silvestrol in infected primary cells by inhibiting eIF4A-dependent viral mRNA translation.

Harvard-Zitierstil: Mueller, C., Schulte, F., Lange-Gruenweller, K., Obermann, W., Madhugiri, R., Pleschka, S., et al. (2018) Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses, Antiviral Research, 150, pp. 123-129. https://doi.org/10.1016/j.antiviral.2017.12.010

APA-Zitierstil: Mueller, C., Schulte, F., Lange-Gruenweller, K., Obermann, W., Madhugiri, R., Pleschka, S., Ziebuhr, J., Hartmann, R., & Gruenweller, A. (2018). Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Research. 150, 123-129. https://doi.org/10.1016/j.antiviral.2017.12.010