3-methylquercetin is a potent and selective inhibitor of poliovirus RNA synthesis

Abstract

3-Methylquercetin (3MQ) is a natural compound isolated from Euphorbia grantii that selectively inhibits poliovirus replication, but has no effect on encephalomyocarditis virus. When the compound is present from the beginning of infection, the bulk of viral protein synthesis is prevented, but the shut-off of host protein synthesis still occurs. Addition of 3MQ 3 hr after infection has a slight effect on viral protein synthesis, suggesting that this compound blocks a step of viral replication different from translation. Indeed, poliovirus RNA synthesis is potently blocked by 3MQ, i.e., 50% inhibition at 2 μg/ml (6.3 × 10 −6 M). No effect on encephalomyocarditis, nor on cellular RNA synthesis is observed even at 20 μ/ml. The inhibitory effect of 3MQ is reversible, since cells treated with this compound from the beginning of infection start to synthesize viral RNA and proteins when the compound is removed. Strikingly, other natural compounds structurally related to 3-methylquercetin such as quercetin, naringenin, naringin, morin, catechin, kaempferol, myricetin, phloretin, phlorizdin, and rutin do not block poliovirus replication.