About: Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses

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About: Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses
Creator	Ziebuhr, John Grünweller, Arnold Müller, Christin Pleschka, Stephan Madhugiri, Ramakanth Lange-Grünweller, Kerstin Obermann, Wiebke Hartmann, Roland Schulte, Falk
Source	Elsevier; Medline; PMC
abstract	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) A1 and poliovirus type 1 (PV), representing different species in the genus Enterovirus (family Picornaviridae), 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 A1 indicates a less critical role of eIF4A activity in HRV A1 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.
has issue date	2018-02-28(xsd:dateTime)
bibo:doi	10.1016/j.antiviral.2017.12.010
bibo:pmid	29258862
has license	els-covid
sha1sum (hex)	d0a747c6e7bcbba0cf55a4924cc16dfda463dbb9
schema:url	https://doi.org/10.1016/j.antiviral.2017.12.010
resource representing a document's title	Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses
has PubMed Central identifier	PMC7113723
has PubMed identifier	29258862
schema:publication	Antiviral Research
resource representing a document's body	covid:d0a747c6e7bcbba0cf55a4924cc16dfda463dbb9#body_text
is schema:about of	named entity 'PICORNAVIRUSES' named entity 'CORONA' named entity 'broad-spectrum' named entity 'compound' named entity 'The higher' named entity 'RNA' named entity 'MERS-CoV' named entity 'cells' named entity 'eIF4A' named entity 'MEDIATED' named entity 'CELLS' named entity 'HERE' named entity 'KNOWN' named entity '80%' named entity 'PATHOGENIC' named entity '100' named entity 'USING' named entity 'STRAND' named entity 'INTERNAL RIBOSOMAL ENTRY SITE' named entity 'SPECIES' named entity 'SPECIFIC' named entity 'INDEPENDENT' named entity 'TAKEN' named entity 'RECENTLY' named entity 'CORONAVIRUSES' named entity 'SPECTRUM' named entity 'STRATEGIES' named entity 'MACROPHAGES' named entity 'ANTIVIRAL ACTIVITY' named entity 'MRC-5' named entity 'VIRAL MRNA TRANSLATION' named entity 'RNA VIRUSES' named entity 'ANTIVIRAL' named entity 'FOUND' named entity 'REVEAL' named entity 'POLIOVIRUS TYPE 1' named entity 'USE' named entity 'ACTIVITIES' named entity 'NONSTRUCTURAL PROTEINS' named entity 'BROAD' named entity 'PICORNAVIRUSES' named entity 'DEPENDENT' named entity 'ANTIVIRAL ACTIVITY' named entity 'CRITICAL' named entity '1.3' named entity 'PRIMARY CELLS' named entity 'INFECTED HUMAN' named entity 'MEASURED' named entity 'VIRUSES' named entity 'INFECTED' named entity 'DUAL' named entity 'MECHANISM' named entity 'CAP' named entity 'INHIBITOR' named entity 'PLANT' named entity 'COMPOUND' named entity 'EFFECTS' named entity 'DIFFERENT' named entity 'EBOLA VIRUS' named entity 'DATA' named entity 'PICORNAVIRIDAE' named entity 'EIF4A' named entity 'HCOV-229E' named entity 'EMBRYONIC' named entity 'GENUS ENTEROVIRUS' named entity 'PERIPHERAL BLOOD MONONUCLEAR CELLS' named entity 'EMPLOY' named entity 'VALUE' named entity 'VALUES' named entity 'BROAD' named entity 'TYPE' named entity 'INHIBITING' named entity 'EXPRESSION'

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