Flavonoids: Potent Inhibitors of Poliovirus RNA Synthesis

Abstract

Some naturally occurring flavonoids, such as 3-methyl quercetin and Ro-090179, show potent anti-picornavirus activity. They inhibit poliovirus replication at concentrations 100-fold or 1000-fold lower than hydroxybenzyl-benzimidazole (HBB) and guanidine, respectively. Ro-090179 selectively blocks viral RNA synthesis in poliovirus-infected HeLa cells more strongly than 3-methyl quercetin and is therefore the most potent and selective inhibitor of poliovirus RNA synthesis described until now. In addition, Ro-090179 discriminates in its inhibition between plus- and minus-stranded RNA synthesis. Thus, analysis of the viral RNA made in poliovirus-infected cells when the compound is added late in the infection cycle, indicates that the synthesis of genomic RNA is potently blocked, whereas minus-stranded RNA synthesis is not inhibited. These findings make Ro-090179 a valuable compound for obtaining insight into the molecular mechanisms of poliovirus RNA replication.