A novel chloro-substituted pentenamide from the fruiting bodies of Amanita virgineoides.

One unusual chloro-substituted pentenamide, (3R)-4-chloro-3-hydroxy-4-pentenamide (1), together with 11 known compounds (2-12) were isolated from the fruiting bodies of Amanita virgineoides. The structure of 1 including the absolute configuration was characterized by extensive spectroscopic analyses and quantum calculation. Compound 1 displayed no obvious activity against herpes simplex virus (HSV), human enterovirus 71 (EV71) or coxsackievirus B3 (CVB3).

Inhibition of enterovirus 71 replication by chrysosplenetin and penduletin.

In recent years, enterovirus 71 (EV71) infections have caused an increasing epidemic in young children, accompanying with more severe nervous system disease and more deaths. Unfortunately, there is no specific medication for it so far. Here we investigated the anti-EV71 activity of chrysosplenetin and penduletin, two o-methylated flavonols isolated from the leaves of Laggera pterodonta. These two compounds were found to have strong activity in vitro against EV71 with low cytotoxicity. In the cytopathic effect (CPE) inhibition assays, both plaque reduction assay and virus yield inhibition assay, the compounds showed a similar 50% inhibitory concentration (IC(50)) value of about 0.20 µM. The selectivity indices (SI) of chrysosplenetin and penduletin were 107.5 and 655.6 in African green monkey kidney (Vero) cells, and 69.5 and 200.5 in human rhabdomyosarcoma (RD) cells, accordingly. The preliminary mechanism analysis indicates that they function not through blocking virus entry or inactivating virus directly but inhibiting viral RNA replication. In the time-of-addition assay, both compounds inhibited progeny virus production and RNA replication by nearly 100% when introduced within 4h post infection. In addition to EV71, both compounds inhibited several other human enteroviruses with similar efficacy. These findings provide a significant lead for the discovery of anti-EV71 drug.