Exploration for anti-enterovirus compounds and analysis on the mechanism of its inhibitory effect on virus infection

Poliovirus (PV) is a small non-enveloped virus belonging to the family Picornaviridae, and is the causative agent of poliomyelitis. With established vaccines, the global eradication program for poliomyelitis is ongoing by the World Health Organization since 1988. In the eradication program, antivirals are anticipated to have some roles in the endgame and post-eradication era of PV. During our search for potent anti-PV compounds, we identified candidate compounds that are associated with a common resistance mutation in viral protein 3A similar to enviroxime (designated as enviroxime-like compounds). Recently, PIK93, an inhibitor of host phosphatidylinositol 4-kinase III beta (PI4KB), was identified as a potent anti-enterovirus compound (Hsu et al., Cell 141:799-811). We found that PIK93 is an enviroxime-like compound, and showed that T-00127-HEV1, which is a novel enviroxime-like compound identified in high-throughput screening, is a specific PI4KB inhibitor. We also showed that PI4KB is an enterovirus-specific host factor required for its viral RNA replication. Analysis of anti-enterovirus compounds would unravel novel host factors that could serve as promising antiviral targets of prophylaxis and therapy of the infection.