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Article Dans Une Revue Cell Chemical Biology Année : 2022

Identifying enhancers of innate immune signaling as broad-spectrum antivirals active against emerging viruses

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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 broadspectrum 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.
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hal-04322328 , version 1 (04-12-2023)

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Ghizlane Maarifi, Marie-France Martin, Abderezak Zebboudj, Aude Boulay, Pierre Nouaux, et al.. Identifying enhancers of innate immune signaling as broad-spectrum antivirals active against emerging viruses. Cell Chemical Biology, 2022, 29 (7), pp.1113-1125.e6. ⟨10.1016/j.chembiol.2022.05.009⟩. ⟨hal-04322328⟩
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