Influenza Virus Entry and Replication Inhibited by 8-Prenylnaringenin from Citrullus Lanatus Var. Citroides (Wild Watermelon)

Abstract We previously demonstrated the anti-influenza activity of Citrullus lanatus var. citroides (wild watermelon, WWM); however, the active ingredient was unknown. Here, we performed metabolomic analysis to evaluate the ingredients of WWM associated with antiviral activity. Many low-molecular-weight compounds were identified, with flavonoids accounting for 3% of all the compounds in WWM juice. Prenylated flavonoids accounted for 13% of the flavonoids. Among the ingredients, 8-prenylnaringenin exhibited the highest antiviral activity. We synthesized 8-prenylnaringenin and used liquid chromatography-mass spectrometry to quantitate the active ingredient in WWM. The antiviral activities of 8-prenylnaringenin were observed against H1N1 influenza subtypes, including oseltamivir-resistant H1N1 viruses, but not against an influenza B virus. Moreover, 8-prenylnaringenin was found to inhibit virus adsorption and late-stage virus replication, suggesting that the mechanisms of action of 8-prenylnaringenin may differ from those of amantadine and oseltamivir. This is the first report on the anti-influenza virus activity of 8-prenylnaringenin. Our results highlight the potential of WWM in developing effective prophylactic and therapeutic approaches against influenza viruses.