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Phosphatidylinositol 4-kinase III Beta Is the Target of Oxoglaucine and Pachypodol (Ro 09-0179) for Their Anti-Poliovirus Activities, and Is Located at Upstream of the Target Step of Brefeldin A

Phosphatidylinositol 4-kinase III Beta Is the Target of Oxoglaucine and Pachypodol (Ro 09-0179) for Their Anti-Poliovirus Activities, and Is Located at Upstream of the Target Step of Brefeldin A

Minetaro Arita, Stefan Philipov, Angel S Galabov

Microbiol Immunol. 2015 Jun;59(6):338-47.

PMID: 25891300

Abstract:

In recent years, phosphatidylinositol 4-kinase III beta (PI4KB) has emerged as a conserved target of anti-picornavirus compounds. In the present study, PI4KB was identified as the direct target of the plant-derived anti-picornavirus compounds, oxoglaucine and pachypodol (also known as Ro 09-0179). PI4KB was also identified as the target via which pachypodol interferes with brefeldin A (BFA)-induced Golgi disassembly in non-infected cells. Oxysterol-binding protein (OSBP) inhibitor also has interfering activity against BFA. It seems that this interference is not essential for the anti-poliovirus (PV) activities of BFA and PI4KB/OSBP inhibitors. BFA inhibited early to late phase PV replication (0 to 6 hr postinfection) as well as PI4KB inhibitor, but with some delay compared to guanidine hydrochloride treatment. In contrast with PI4KB/OSBP inhibitors, BFA inhibited viral nascent RNA synthesis, suggesting that BFA targets some step of viral RNA synthesis located downstream of the PI4KB/OSBP pathway in PV replication. Our results suggest that PI4KB is a major target of anti-picornavirus compounds identified in vitro for their anti-picornavirus activities and for some uncharacterized biological phenomena caused by these compounds, and that BFA and PI4KB/OSBP inhibitors synergistically repress PV replication by targeting distinct steps in viral RNA replication.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP33708724	Pachypodol		33708-72-4	Price

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