About: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication Goto Sponge NotDistinct Permalink

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication
Creator	Chattopadhyay, Saurabh Chakravarti, Ritu Chawla, Karan Ciricillo, Jacob Fabry, Stephanie Garcia, Julie Glanz, Anna Jay, Bryanna Subramanian, Gayatri Taylor, R
source	PMC
abstract	Interferon (IFN) regulatory factor 3 (IRF3) is the key transcription factor for the induction of IFN and antiviral genes. The absence of antiviral genes in IRF3 deficiency leads to susceptibility to a wide range of viral infections. Previously, we uncovered a function for nontranscriptional IRF3 (nt-IRF3), RLR (RIG-I-like receptor)-induced IRF3-mediated pathway of apoptosis (RIPA), which triggers apoptotic killing of virus-infected cells. Using knock-in mice expressing a transcriptionally inactive, but RIPA-active, IRF3 mutant, we demonstrated the relative contribution of RIPA to host antiviral defense. Given that RIPA is a cellular antiviral pathway, we hypothesized that small molecules that promote RIPA in virus-infected cells would act as antiviral agents. To test this, we conducted a high throughput screen of a library of FDA-approved drugs to identify novel RIPA activators. Our screen identified doxorubicin as a potent RIPA-activating agent. In support of our hypothesis, doxorubicin inhibited the replication of vesicular stomatitis virus, a model rhabdovirus, and its antiviral activity depended on its ability to activate IRF3 in RIPA. Surprisingly, doxorubicin inhibited the transcriptional activity of IRF3. The antiviral activity of doxorubicin was expanded to flavivirus and herpesvirus that also activate IRF3. Mechanistically, doxorubicin promoted RIPA by activating the extracellular signal-regulated kinase (ERK) signaling pathway. Finally, we validated these results using another RIPA-activating compound, pyrvinium pamoate, which showed a similar antiviral effect without affecting the transcriptional activity of IRF3. Therefore, we demonstrate that the RIPA branch of IRF3 can be targeted therapeutically to prevent virus infection.
has issue date	2020-04-14(xsd:dateTime)
bibo:doi	10.3390/v12040442
bibo:pmid	32295140
has license	cc-by
sha1sum (hex)	d7645f3976d04b8ffe3ae2b0fe2cc604c6774ce0
schema:url	https://doi.org/10.3390/v12040442
resource representing a document's title	High Throughput Screening of FDA-Approved Drug Library Reveals the Compounds that Promote IRF3-Mediated Pro-Apoptotic Pathway Inhibit Virus Replication
has PubMed Central identifier	PMC7232324
has PubMed identifier	32295140
schema:publication	Viruses
resource representing a document's body	covid:d7645f3976d04b8ffe3ae2b0fe2cc604c6774ce0#body_text
is schema:about of	named entity 'demonstrate' named entity 'IRF3' named entity 'IRF3' named entity 'IRF3' named entity 'drugs' named entity 'host' named entity 'viral infections' named entity 'activity' named entity 'cells' named entity 'High' named entity 'inhibited' named entity 'IRF3' named entity 'RIPA' named entity 'Our' named entity 'prevent' named entity 'demonstrated' named entity 'Interferon' named entity 'doxorubicin' named entity 'transcription factor' named entity 'cellular' named entity 'ERK' named entity 'RLR' named entity 'activate' named entity 'expanded' named entity 'RIPA' named entity 'leads' named entity 'antiviral' named entity 'induced' named entity 'targeted' named entity 'antiviral' named entity 'IFN' named entity 'transcriptional activity' named entity 'signaling pathway' named entity 'RIPA' named entity 'small molecules' named entity 'doxorubicin' named entity 'doxorubicin' named entity 'herpesvirus' named entity 'IRF3' named entity 'viral infections' named entity 'antiviral agents' named entity 'RIG-I-like receptor' named entity 'mice' named entity 'absence' named entity 'infection' named entity 'IRF3' named entity 'Irf3' named entity 'doxorubicin' named entity 'doxorubicin' named entity 'cytosolic' named entity 'RIPA' named entity 'GFP fluorescence' named entity 'antiviral activity' named entity 'transfection' named entity 'RIPA' named entity 'immunoblot' named entity 'protein' named entity 'virus infection' named entity 'doxorubicin' named entity 'doxorubicin' named entity 'extracellular signal-regulated kinase' named entity 'IRF3' named entity 'viral protein' named entity 'HSV-1' named entity 'viral protein' named entity 'RIPA' named entity 'RIPA' named entity 'doxorubicin' named entity 'topotecan' named entity 'IRF3' named entity 'Cas9' named entity 'protein'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software