Effects and mechanism of 3,5,6,7,4'-pentamethoxyflavone for blocking arenavirus entry

Arenaviruses are enveloped RNA viruses, and eight members in this family are known to cause human hemorrhagic fever. Treatments for the viral hemorrhagic fever (VHF) by arenaviruses are very limited. We have identified the first flavone, tangeretin, with broad-spectrum inhibitory activities on VHF-arenaviruses infection by blocking viral entry. In this study, we evaluated thirty-four tangeretin analogues and found 3,5,6,7,4'-pentamethoxyflavone as a Lassa virus entry inhibitor, with EC₅₀ of 5.2 μmol·L^-1, by blocking the viral fusion pro cess. The compound 3,5,6,7,4'-pentamethoxyflavone is effective on all known VHF-arenaviruses, with EC₅₀ range of 0.84-10.2 μmol·L^-1. These results suggest that 3,5,6,7,4'-pentamethoxyflavone is able to serve as a start point for discovery of arenavirus entry inhibitors from flavone natural products.