Mumefural and related HMF derivatives from Japanese apricot fruit juice concentrate show multiple inhibitory effects on pandemic influenza A (H1N1) virus

► Five compounds were isolated from fruit-juice concentrate of Japanese apricot. ► Four HMF derivatives, but not HMF, exhibited lectin-like activity. ► Mumefural and its derivative can abolish hemagglutination of influenza virus. ► Mumefural was the most active anti-sialidase compound of all five isolated compounds. ► Mumefural inhibited the growth of a novel pandemic 2009 H1N1 virus in cell culture. Fruit-juice concentrate of Japanese apricot (Prunus mume Sieb. et Zucc.) has been shown to be effective against influenza A infection in MDCK cells. In this study, we isolated five components from the fruit-juice concentrate of Japanese apricot, 5-(hydroxymethyl)-2-formylfuran (HMF), 1-[5-(2-formylfuryl)methyl]dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate (mumefural, MF), 2-[5-(2-formylfuryl)methyl]dihydrogen 2-hydroxypropane-1,2,3-tricarboxylate (MF‘), 1-[5-(2-formylfuryl)methyl]hydrogen 1-hydroxyethane-1,2-dicarboxylate (MA1) and 2-[5-(2-formylfuryl)methyl]hydrogen 1-hydroxyethane-1,2-dicarboxylate (MA2), and investigated their inhibitory activities against the novel influenza A/Narita/1/2009 (H1N1) pandemic virus hemagglutinin and neuraminidase functions, which are essential for viral attachment and budding, respectively. An hemagglutination inhibition assay indicated that MF and MF‘ were effective at minimum hemagglutination concentrations of 3.1 and 6.3mM, respectively. An inhibition study for sialidase activity of the neuraminidase spike showed that MF was the most active anti-sialidase compound with an IC50 value of 0.21±0.01mM, followed by MA2 (IC50, 0.71±0.09mM), MA1 (IC50, 1.64±0.31mM) and MF‘(IC50, 1.62±0.22mM). Furthermore, MF was shown to inhibit the growth of the pandemic virus in a dose-dependent manner (62±3% inhibition at 5mM). The results suggest that MF, a citric acid ester linked to HMF at the 1-position of the propane backbone, might be a lead compound for the development of anti-influenza A inhibitors.