FGF receptor kinase inhibitors exhibit broad antiviral activity by targeting Src family kinases
A recent "Cellular and Molecular Life Sciences" paper by the Werner group (IMHS) identifies broad-spectrum antiviral activities of FGF receptor kinase inhibitors, which involve their unexpected effect on Lyn kinase. These data suggest Lyn as a promising target for the treatment of viral infections.
The recent COVID-19 pandemic has highlighted the need for efficient and broad-spectrum antiviral therapies. Unfortunately, most of the available therapeutics are virus-specific or have high toxicity.
Researchers at IMHS discovered that several fibroblast growth factor receptor (FGFR) inhibitors, which are in clinical trials for the treatment of certain types of cancer, inhibit infection of different cell types with different DNA and RNA viruses by blocking the early stages of the viral life cycle. Surprisingly, their antiviral activity was largely independent of FGFR kinase inhibition. Using bioinformatics analysis of kinome data, targeted kinase assays, siRNA-mediated knock-down and pharmacological inhibition experiments, the authors showed that blockade of Src family kinases, in particular Lyn, is mainly responsible for the antiviral activity of FGFR inhibitors. These results offer interesting therapeutic opportunities and provide insight into the action of tyrosine kinase inhibitors in viral infection. The identification of an important role of Lyn in the activity of some FGFR kinase inhibitors should also be considered when these compounds are used for the treatment of cancer and other diseases associated with increased FGFR kinase activity.
Link to the paper in "external page Cellular and Molecular Life Sciences".