Targeting PI4KB and Src/Abl host kinases as broad-spectrum antiviral strategy: myth or real opportunity?

Abstract

Viruses pose a continuous threat to human health. Limited treatment options exist for current viruses, and the risk of infections with newly emerging or re-emerging viruses is increasing. In a pandemic scenario, having a broad-spectrum antiviral to limit viral spread while developing specific antivirals and vaccines is crucial. Targeting host kinases represents a valuable strategy due to the higher barrier to resistance and the broad-spectrum activity it offers. While cells have redundant kinases for the same biological function, viruses rely on specific kinases for their replication cycle, enabling targeted antiviral action with limited toxicity. This review focuses on two extensively studied kinase targets: the lipid kinase phosphatidylinositol 4-kinase IIIβ (PI4KB) and the tyrosine kinase proteins Src and Abl. Compounds active against these targets are reviewed in terms of the viruses they inhibit, their mechanisms of action and their stage of development. While PI4KB inhibitors have reached clinical trials, those targeting Src and Abl remain largely in the preclinical phase. Nevertheless, opportunities exist to improve potency and further understand the specific roles of these kinases in the life cycle of multiple viruses.