Identifying enhancers of innate immune signaling as broad-spectrum antivirals active against emerging viruses.
Cell Chem Biol
; 29(7): 1113-1125.e6, 2022 07 21.
Article
in English
| MEDLINE | ID: covidwho-1894864
ABSTRACT
The increasingly frequent outbreaks of pathogenic viruses have underlined the urgent need to improve our arsenal of antivirals that can be deployed for future pandemics. Innate immunity is a powerful first line of defense against pathogens, and compounds that boost the innate response have high potential to act as broad-spectrum antivirals. Here, we harnessed localization-dependent protein-complementation assays (called Alpha Centauri) to measure the nuclear translocation of interferon regulatory factors (IRFs), thus providing a readout of innate immune activation following viral infection that is applicable to high-throughput screening of immunomodulatory molecules. As proof of concept, we screened a library of kinase inhibitors on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and identified Gilteritinib as a powerful enhancer of innate responses to viral infection. This immunostimulatory activity of Gilteritinib was found to be dependent on the AXL-IRF7 axis and results in a broad and potent antiviral activity against unrelated RNA viruses.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Virus Diseases
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Cell Chem Biol
Year:
2022
Document Type:
Article
Affiliation country:
J.chembiol.2022.05.009
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