About: Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication

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About: Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication 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	Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
Creator	Kehn-Hall, Kylene Lundberg, Lindsay Pinkham, Chelsea Bell, Todd Brahms, Ashwini Woodson, Caitlin Bailey, Charles Espina, Virginia Carey, Brian Lin, Liotta, Lance Dahal, De La Fuente, Cynthia Id, Bibha Id, Shih-Chao
Source	Medline; PMC
abstract	Viruses must parasitize host cell translational machinery in order to make proteins for viral progeny. In this study, we sought to use this signal transduction conduit against them by inhibiting multiple kinases that influence translation. Previous work indicated that several kinases involved in translation, including p70 S6K, p90RSK, ERK, and p38 MAPK, are phosphorylated following Rift Valley fever virus (RVFV) infection. Furthermore, inhibiting p70 S6K through treatment with the FDA approved drug rapamycin prevents RVFV pathogenesis in a mouse model of infection. We hypothesized that inhibiting either p70 S6K, p90RSK, or p90RSK’s upstream kinases, ERK and p38 MAPK, would decrease translation and subsequent viral replication. Treatment with the p70 S6K inhibitor PF-4708671 resulted in decreased phosphorylation of translational proteins and reduced RVFV titers. In contrast, treatment with the p90RSK inhibitor BI-D1870, p38MAPK inhibitor SB203580, or the ERK inhibitor PD0325901 alone had minimal influence on RVFV titers. The combination of PF-4708671 and BI-D1870 treatment resulted in robust inhibition of RVFV replication. Likewise, a synergistic inhibition of RVFV replication was observed with p38MAPK inhibitor SB203580 or the ERK inhibitor PD0325901 combined with rapamycin treatment. These findings serve as a proof of concept regarding combination kinase inhibitor treatment for RVFV infection.
has issue date	2018-04-13(xsd:dateTime)
bibo:doi	10.3390/v10040191
bibo:pmid	29652799
has license	cc-by
sha1sum (hex)	369914e87f682579eb3a5efeb43dc0184a88b5d6
schema:url	https://doi.org/10.3390/v10040191
resource representing a document's title	Combination Kinase Inhibitor Treatment Suppresses Rift Valley Fever Virus Replication
has PubMed Central identifier	PMC5923485
has PubMed identifier	29652799
schema:publication	Viruses
resource representing a document's body	covid:369914e87f682579eb3a5efeb43dc0184a88b5d6#body_text
is schema:about of	named entity 'ERK' named entity 'rapamycin' named entity 'reduced' named entity 'translation' covid:arg/369914e87f682579eb3a5efeb43dc0184a88b5d6 named entity 'combination' named entity 'p90RSK' named entity 'machinery' named entity 'S6K' named entity 'S6K' named entity 'replication' named entity 'replication' named entity 'Rift Valley' named entity 'viral' named entity 'signal transduction' named entity 'parasitize' named entity 'inhibition' named entity 'study' named entity 'p90RSK' named entity 'Viruses' named entity 'pathogenesis' named entity 'RVFV' named entity 'approved drug' named entity 'p70 S6K' named entity 'RVFV' named entity 'infection' named entity 'Rift Valley fever virus' named entity 'RVFV' named entity 'p90RSK' named entity 'kinases' named entity 'RVFV' named entity 'Kinase Inhibitor' named entity 'cell' named entity 'homeostasis' named entity 'La Jolla' named entity 'RVFV' named entity 'chemotherapy' named entity 'supernatants' named entity 'RVFV' named entity 'SB203580' named entity 'p90RSK' named entity 'kinase' named entity 'kinase' named entity 'ATCC' named entity 'rapamycin' named entity 'phosphorylation' named entity 'rapamycin' named entity 'p90RSK' named entity 'p38 MAPK' named entity 'RVFV' named entity 'ribosomal protein' named entity 'Phosphorylation' named entity 'ATCC' named entity 'RVFV' named entity 'hepatitis viruses' named entity 'Rapamycin' named entity 'gene' named entity 'p38 MAPK' named entity 'actin' named entity 'ribosomal protein' named entity 'hepatocyte' named entity 'SB203580' named entity 'kinase' named entity 'p90RSK' named entity 'carboxy-terminal' named entity 'chemotherapy' named entity 'MOI'

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