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

Castrillo, José Luis; Berghe, Dirk Vanden; Carrasco, Luís

doi:10.1016/0042-6822(86)90386-7

Cited by 80 publications

(52 citation statements)

References 11 publications

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“…They are not virucidal, but interfere with the replication of several viruses, including poliovirus (Ishitsuka et al, 1982;Van Hoof et al, 1984;Castrillo et al, 1986;Vrijsen et al, 1987). An anti-poliovirus activity of quercetin itself, i.e.…”

Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Flavones and Potentiation by Ascorbate

Vrijsen

Everaert

Boeyé

1988

Journal of General Virology

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SUMMARYWe compared the anti-poliovirus activities of three flavones, quercetin, luteolin and 3-methylquercetin, which differ only at ring position 3. 3-Methylquercetin was the most potent compound. Quercetin exhibited antiviral activity only when protected against oxidative degradation by ascorbate. The antiviral activity of luteolin was comparable to that of ascorbate-stabilized quercetin.Several 3-methoxy derivatives of quercetin (3,3',4',5,7-pentahydroxyflavone) extracted from various plants are known to exhibit antiviral activity. They are not virucidal, but interfere with the replication of several viruses, including poliovirus (Ishitsuka et al., 1982;Van Hoof et al., 1984;Castrillo et al., 1986;Vrijsen et al., 1987). An anti-poliovirus activity of quercetin itself, i.e. a direct virucidal effect as well as interference with plaque formation, has been shown recently (Kaul et al., 1985). However, these results are at variance with previous reports according to which quercetin was virucidal only to enveloped, but not to unenveloped viruses (B61adi et al., 1977;Veckenstedt & Pusztai, 1981).The discrepancies about the antiviral properties of quercetin may originate in the oxidative degradation of this flavone in aqueous solution (Nishinaga et aL, 1979;Rajananda & Brown, 1981). In this communication, the anti-poliovirus activity of quercetin was determined in the presence and absenceof the antioxidant ascorbate. Comparative experiments were also carried out with 3-methylquercetin and luteolin, which differ from quercetin only at ring position 3 (Fig. 1).The antiviral effect of quercetin, luteolin and 3-methylquercetin was tested by the plaque reduction assay (Fig. 2). Both luteolin (not previously reported to possess antiviral activity) and 3-methylquercetin were active; 40 ktM-luteolin or 10 ktu-3-methylquercetin reduced the plaque count by half. Quercetin was inactive, even at the highest concentration tested (100 p,M). However, in the presence of ascorbate it did cause plaque reduction and this enhancement of its activity reached saturation at an ascorbate concentration of 100 ~tM. D-and L-ascorbate were equivalent, whereas dehydroascorbate was inactive (Fig. 3). Ascorbate alone failed to show any antiviral activity.With maximum enhancement by ascorbate, 30 ~tM-quercetin caused 50 % plaque reduction; this figure is close to that previously noted for luteolin (Fig. 2b). The antiviral effect of luteolin OH HO~R~OH OH o 0000-8341 © 1988 SGM

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Section: Discussionmentioning

confidence: 99%

Antiviral Activity of Flavones and Potentiation by Ascorbate

Vrijsen

Everaert

Boeyé

1988

Journal of General Virology

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“…Several hydroxylated and methoxylated flavonoids block the infection of a wide range of DNA and RNA viruses (Kaul et al 1985); preliminary studies on structure-activity relationships that indicated that a 3-methoxy group in the flavone skeleton is important for strong picornavirus inhibition (Van Hoof et al, 1984;Tsuchiya et al, 1985). Although the mechanism is not completely understood, natural flavonoids have been found to interfere with an early step in viral RNA synthesis, apparently by a selective inhibition of the synthesis of genomic RNA (Castrillo et al, 1986;Gonzales et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

In vitro Evaluation of the Anti-Picornavirus Activities of New Synthetic Flavonoids

Desideri

Conti

Sestili

et al. 1995

Antivir Chem Chemother

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SummarySubstituted oxazolinylflavons and oxazolinylflavanones were synthesized in order to compare their anti-picornavirus activities with those of related natural and synthetic compounds. The antiviral potencies of the new compounds were evaluated against rhinovirus type 1B and poliovirus type 2 by a plaque reduction assay in HeLa cell cultures. Among the substituted flavanones only 6-chloro-4'-oxazolinylflavanone showed activity against both viruses. A comparison of the effects of 3-substituted f1avones indicated that the presence of a 3-methoxy group enhances the activity against rhinovirus, while the presence of a 3-hydroxy group enhances the activity against poliovirus.

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“…The gels were placed in a microwave oven (Sharp R-8000E) and dried in only 6 min as described previously (Castrillo et al, 1986). The dried gels were exposed using RP X-ray films (MAFE).…”

Section: Methodsmentioning

confidence: 99%

The P2 and P3 Regions of the Poliovirus Genome are Preferentially Translated at Alkaline pH in Infected HeLa Cells

Castrillo

Urzainqui

Carrasco

1988

Journal of General Virology

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SUMMARYHeLa cells infected with poliovirus exclusively synthesized proteins coded by the P2 and P3 regions of the viral genome when they were placed in an alkaline medium lacking sodium ions. The amount of viral protein synthesized was augmented by increasing the concentration of KC1. Also in the presence of KC1, the ceils continued synthesizing this altered pattern of proteins for longer times. This effect occurred in the presence of guanidine, it was reversible, and the normal pattern of poliovirus proteins reappeared when control medium was added, even when guanidine was present. These findings suggest that truncated viral RNA is not made under these conditions. Pactamycin and sodium fluoride, two known inhibitors of the initiation of translation, blocked protein synthesis in cells placed in alkaline medium, indicating the possibility that initiation at internal sites of the viral mRNA may take place under these conditions. Finally, the proteins synthesized were analysed by two-dimensional gel electrophoresis. The proteins migrated as authentic viral proteins indicating that if internal initiation takes place, at least some of these initiation events occur in phase with the initiation codon present in the poliovirus genome.

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

Cited by 80 publications

References 11 publications

Antiviral Activity of Flavones and Potentiation by Ascorbate

Antiviral Activity of Flavones and Potentiation by Ascorbate

In vitro Evaluation of the Anti-Picornavirus Activities of New Synthetic Flavonoids

The P2 and P3 Regions of the Poliovirus Genome are Preferentially Translated at Alkaline pH in Infected HeLa Cells

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