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In vitro antiviral activities of three flavonoids; fisetin, naringenin and rutin against DENV-2 (NGC strain) were evaluated. Inhibitory effects of each compound at the different stages of DENV-2 infection were examined using foci forming unit reduction assay (FFURA) and quantitative real-time polymerase chain amplification (qRT-PCR). Fisetin, rutin and naringenin showed cytotoxic effects against Vero cells with 50% cytotoxicity (CC50 ) values of 247, >1000, and 87 µg/mL, respectively. Fisetin when added to Vero cells after virus adsorption inhibited DENV replication with a half maximal inhibition concentration (IC50 ) value of 55 µg/mL and selectivity index (SI) of 4.49. The IC50 value of fisetin was 43.12 µg/mL with SI=5.72 when Vero cells were treated for 5 h before virus infection and continuously up to 4 days postinfection. There was no direct virucidal activity or prophylactic activity of fisetin against DENV-2. Rutin and naringenin did not inhibit DENV-2 replication in Vero cells. Naringenin however, exhibited direct virucidal activity against DENV-2 with IC50 = 52.64 µg/mL but the SI was <1. The present study suggests that among the flavonoids examined, only fisetin showed significant in vitro anti dengue virus replication activity.

In vitro antiviral activity of fisetin, rutin and naringenin against dengue virus type-2