What is it about?
We identified PI4KB as the target of previously reported anti-enterovirus compounds, oxoglaucine and Ro 09-0179 for their anti-enterovirus activity. We also showed that 1) PI4KB/OSBP inhibitors suppress Golgi disassembly induced by brefeldin A, as previously reported for Ro 09-0179, and 2) brefeldin A inhibited viral nascent RNA synthesis in contrast to PI4KB/OSBP inhibitors, which suppress formation of viral replication complex but not nascent RNA synthesis.
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Why is it important?
Results of this study suggested a working hypothesis: "All the non-cytotoxic, host-activity-targeting anti-enterovirus compounds identified in vitro are enviroxime-like compounds in terms of the resistance mutation and/or targeting the PI4KB/OSBP pathway”, which we named "enviroxime hypothesis".
Perspectives
It seemed to me surprising that candidate host targets for anti-enterovirus drug might be quite limited, possibly to PI4KB/OSBP pathway. This hypothesis holds true in our recent analysis of an anti-enterovirus compound MDL-860, which does not inhibit in vitro Pi4KB activity, but targets in vivo PI4KB activity via allosteric regulation by covalent modification of C646 of PI4KB (Arita et al., 2017, ACS Infect Dis).
Dr Minetaro Arita
National Institute of Infectious Diseases
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This page is a summary of: 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, Microbiology and Immunology, June 2015, Wiley,
DOI: 10.1111/1348-0421.12261.
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