About: Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol

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About: Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol
Creator	Ziebuhr, John Glitscher, Mirco Grünweller, Arnold Hildt, Eberhard Müller, Christin Elgner, Fabian Oestereich, Lisa Lange-Grünweller, Kerstin Obermann, Wiebke Singh, Kamini Wendel, Hans-Guido Hartmann, Roland Schulte, Falk
Source	Elsevier; Medline; PMC
abstract	Rocaglates, a class of natural compounds isolated from plants of the genus Aglaia, are potent inhibitors of translation initiation. They are proposed to form stacking interactions with polypurine sequences in the 5′-untranslated region (UTR) of selected mRNAs, thereby clamping the RNA substrate onto eIF4A and causing inhibition of the translation initiation complex. Since virus replication relies on the host translation machinery, it is not surprising that the rocaglate Silvestrol has broad-spectrum antiviral activity. Unfortunately, synthesis of Silvestrol is sophisticated and time-consuming, thus hampering the prospects for further antiviral drug development. Here, we present the less complex structured synthetic rocaglate CR-31-B (−) as a novel compound with potent broad-spectrum antiviral activity in primary cells and in an ex vivo bronchial epithelial cell system. CR-31-B (−) inhibited the replication of corona-, Zika-, Lassa-, Crimean Congo hemorrhagic fever viruses and, to a lesser extent, hepatitis E virus (HEV) at non-cytotoxic low nanomolar concentrations. Since HEV has a polypurine-free 5′-UTR that folds into a stable hairpin structure, we hypothesized that RNA clamping by Silvestrol and its derivatives may also occur in a polypurine-independent but structure-dependent manner. Interestingly, the HEV 5′-UTR conferred sensitivity towards Silvestrol but not to CR-31-B (−). However, if an exposed polypurine stretch was introduced into the HEV 5′-UTR, CR-31-B (−) became an active inhibitor comparable to Silvestrol. Moreover, thermodynamic destabilization of the HEV 5′-UTR led to reduced translational inhibition by Silvestrol, suggesting differences between rocaglates in their mode of action, most probably by engaging Silvestrol's additional dioxane moiety.
has issue date	2020-01-10(xsd:dateTime)
bibo:doi	10.1016/j.antiviral.2020.104706
bibo:pmid	31931103
has license	no-cc
sha1sum (hex)	aa264b65408831a37b2943b60805e3773e0acaa5
schema:url	https://doi.org/10.1016/j.antiviral.2020.104706
resource representing a document's title	Comparison of broad-spectrum antiviral activities of the synthetic rocaglate CR-31-B (−) and the eIF4A-inhibitor Silvestrol
has PubMed Central identifier	PMC7114339
has PubMed identifier	31931103
schema:publication	Antiviral Res
resource representing a document's body	covid:aa264b65408831a37b2943b60805e3773e0acaa5#body_text
is schema:about of	named entity 'nanomolar' named entity 'development' named entity 'broad-spectrum' named entity 'engaging' named entity 'hepatitis E' named entity 'Since' named entity 'interactions' named entity 'surprising' named entity 'translation' named entity 'ANTIVIRAL' named entity 'BROAD' named entity 'SYNTHETIC' named entity 'BROAD' named entity 'REGION' named entity 'TIME-CONSUMING' named entity 'STRUCTURED' named entity 'TRANSLATIONAL INHIBITION' named entity 'INHIBITOR' named entity 'OCCUR' named entity 'SPECTRUM' named entity 'ADDITIONAL' named entity 'CRIMEAN CONGO HEMORRHAGIC FEVER' named entity 'PRIMARY CELLS' named entity 'INHIBITOR' named entity 'INHIBITORS' named entity 'STRETCH' named entity 'LESSER' named entity 'SYNTHETIC' named entity 'REPLICATION' named entity 'INHIBITED' named entity 'CLAMPING' named entity 'STACKING' named entity 'THERMODYNAMIC' named entity 'SYNTHESIS' named entity 'PRESENT' named entity 'TO FORM' named entity 'HEMORRHAGIC FEVER VIRUSES' named entity 'ANTIVIRAL ACTIVITY' named entity 'A CLASS' named entity 'PROBABLY' named entity 'NANOMOLAR' named entity 'PLANTS' named entity 'SILVESTROL' named entity 'ACTIVITIES' named entity 'SELECTED' named entity '27S' named entity 'EX VIVO' named entity '80%' named entity 'MACHINERY' named entity 'SPECTRUM' named entity 'EIF4A' named entity 'COMPLEX' named entity 'ITS' named entity 'MRNAS' named entity 'EXTENT' named entity 'SILVESTROL' named entity 'ENGAGING' named entity 'CAUSING' named entity 'BUT' named entity 'NON-' named entity 'ACTIVE' named entity 'SUBSTRATE' named entity 'MODE OF ACTION' named entity 'CYTOTOXIC' named entity 'EXPOSED' named entity 'ISOLATED' named entity 'COMPARISON' named entity 'CELL SYSTEM' named entity 'INTERACTIONS'

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