Anti-influenza A virus activity of flavonoids in vitro: a structure-activity relationship

Secondary plant metabolites from food extracts, namely daidzein, quercetin, and luteolin, exhibit anti-influenza virus effects, with IC₅₀ values of 143.6, 274.8, and 8.0 μM, respectively. The activities of these metabolites differ depending on the functional groups. Therefore, in this study, we focused on members of the flavonoid group, and investigated the anti-influenza viral effects of different flavonoid classes (flavone, isoflavone, flavonol, flavanone, and flavan-3-ol) in vitro. The IC₅₀ values were 4.9-82.8 μM, 143.6 μM, 62.9-477.8 μM, 290.4-881.1 μM, and 22.9-6717.2 μM, respectively, confirming their activity. The modifying group factors (number, position, type) in the flavonoid skeleton may be significantly related to the anti-influenza virus activity. Moreover, time-of-addition assay revealed that the mechanism of inhibition varied for the different classes; for example, flavonoids that inhibit virus adsorption or the early stage of viral growth. Interestingly, all the examined flavonoids inhibited the late stages of viral growth, suggesting that flavonoids mainly inhibit the late events in viral growth before the release of viral particles. Additionally, apigenin might be effective against oseltamivir-resistant strains. Our results may be important in the development of anti-influenza virus therapeutic strategies in the future.