Flavonoids: Potent Inhibitors of Poliovirus RNA Synthesis

Antiviral chemistry & chemotherapy 12/1990; 1(3):203-209. DOI: 10.1177/095632029000100304


Some naturally occuring 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 valuble compound for obtaining insight into the molecular mechanism of poliovirus RNA replication.

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Available from: Maria Eugenia Gonzalez
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    • "In some other studies revealed that "Natural and synthetic flavonoids and interfere with picornavirus replication leading to preventing of decapsidation of viral particles and RNA release within cells or blocking viral RNA synthesis" (Conti et al., 1990; Genovese et al., 1995; Gonzalez et al., 1990; Salvati et al., 2004). "
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    • "Effect of 3-methylkaempferol on viral RNA synthesis Since a direct action of some flavonoids on viral RNA replication has been previously reported (Castrillo et al., 1986; Castrillo & Carrasco, 1987; Gonzalez et al., 1990; "
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    ABSTRACT: The search for antiviral agents against vesicular stomatitis virus, herpes simplex virus type 1 and poliovirus type 2 in plants extracts, led to the isolation of two antipoliovirus flavonoids from the medicinal plant Psiadia dentata (Cass.) DC, Asteraceae: 3-methylkaempferol and 3,4'-dimethylkaempferol. The antipoliovirus activity of both compounds was estimated by comparison with 3-methylquercetin, guanidine and Ro-090179. The most potent inhibitor of poliovirus replication was 3-methylkaempferol, and therefore we investigated its mechanism of action. We showed, using the inhibition of [3H]uridine incorporation in viral RNA and performing a dot-blot with one RNA probe specific for the poliovirus genomic strand RNA, that 3-methylkaempferol inhibits the genomic RNA synthesis of poliovirus.
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    • "Beside an effect on HRVs, 4′,5-dihydroxy-3,3′,7- trimethoxyflavone (Ro-09-0179) also exerted an inhibitory activity against coxsackieviruses in tissue cultures (Kaul et al., 1985). The mechanism of action of flavonoids has been attributed to interference with an early stage of viral infection , probably represented by viral RNA synthesis (Castrillo et al., 1986; Gonzales et al., 1990). "
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