Phosphatidylinositol 4-kinase III beta (PI4KB)

Phosphatidylinositol 4-kinases (PI4Ks) are involved in the replication of several viruses, including EVs. P14Ks have been identified as potential antiviral targets.

PI4Ks synthesize phosphatidylinositol 4-phosphate, are evolutionarily conserved, and include several human isoforms. They regulate trafficking between the Golgi and the membrane. It has been shown that several RNA viruses, including EV, may hijack PI4Ks and use the PI4K-enriched organelle membranes as replication platforms (

PI4KB, one of the PI4K protein isoforms, has been shown to be important in the replication of EVs specifically, and high levels of this protein are present in EV replication membranes throughout infection. PI4KB was selected as a target for Curovir’s novel EV antivirals based on the anticipation that inhibiting PI4KB would counteract EV infection by preventing the virus from replicating.

We are currently exploring the mechanism by which CUR-N399/PI4KB inhibits RSV.

Apart from PI4KB’s involvement in viral infections, PI4KB has also been implicated in parasitic infections, certain forms of cancer and immunosuppression.

“PI4KB was selected as a target for Curovir’s novel EV antivirals”

PI4KB inhibitors have been evaluated by several companies and one substance, enviroxime, was evaluated in clinical trials during the 1980s. At that time, the mechanism of its anti-EV effect had not been identified and only recently has it been shown that enviroxime acts as a PI3K and PI4K inhibitor. Compared to CUR-N399, enviroxime is both less potent and less selective for PI4KB. Clinical trial results with enviroxime displayed poor oral bioavailability and nasal administration showed limited therapeutic effect on EV infections. In October 2020, GSK started a phase I clinical trial with the PI4KB inhibitor GSK3923868, administered as a powder for inhalation. Also, in May 2021 Kyorin Pharmaceutical initiated a phase I clinical trial with a PI4KB inhibitor KRP-A218.