FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases.

The development of antiviral strategies is a key task of biomedical research, but broad-spectrum virus inhibitors are scarce. Here we show that fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors reduce infection of several cell types with DNA and RNA viruses by blocking early stages of infection, but not viral cell association. Unexpectedly, their antiviral activity was largely independent of FGFR kinase inhibition. RNA profiling showed upregulation of interferon response genes by FGFR inhibitors, but their expression did not correlate with the antiviral activity in infected cells. Using bioinformatics analysis of kinome data, targeted kinase assays, siRNA-mediated knock-down and pharmacological inhibition experiments, we show that blockade of Src family kinases, in particular Lyn, is mainly responsible for the antiviral activity of FGFR inhibitors. These results identify FGFR inhibitors as broad-spectrum antiviral agents and suggest the poorly studied Lyn kinase as a promising target for the treatment of viral infections.
Competing Interests: Declarations. Ethics approval and consent to participate: Human primary keratinocytes were kindly provided by Dr. Hans-Dietmar Beer, University Hospital Zurich. They had been isolated from foreskin of healthy boys, which had been obtained anonymously with parental written consent, as part of the University of Zurich biobank project. The collection and use of samples were approved by the local and cantonal Research Ethics Committees, adhering to the Declaration of Helsinki Principles. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)