In vivo anti-influenza virus activity of plant flavonoids possessing inhibitory activity for influenza virus sialidase.

Isoscutellarein (5,7,8,4'-tetrahydroxyflavone) from the leaf of Scutellaria baicalensis non-competitively inhibited (IC50, 20 microM) the hydrolysis of sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate by influenza virus sialidase with an apparent Ki value of 41 microM. Negligible inhibitory activity was observed for mouse liver sialidase at a concentration of 79 microM. Isoscutellarein also inhibited the replication of influenza virus A/WSN/33 in Madin-Darby bovine kidney cells with 50% virus inhibitory dose at 16 nmol/well and influenza virus A/PR/8/34 in the allantoic sac of embryonated egg with little toxic effects. The flavone showed significant anti-influenza virus activity in vitro similar to isoscutellarein-8-methylether (F36) (Nagai, T., Miyaichi, Y., Tomimori, T., Suzuki, Y. and Yamada H., 1990, Chem. Pharm. Bull. 38, 1329-1332), and more potent virucidal activity in ovo than F36. However, F36 completely prevented proliferation of mouse-adapted influenza virus A/PR/8/34 in mouse lung by the intranasal (0.5 mg/kg) and intraperitoneal (4 mg/kg) administrations, and it was more potent than the known anti-influenza virus substance, amantadine. Intranasal administration of F36 (0.5 mg/kg) also protected mice against a lethal influenza virus A/PR/8/34 infection. Isoscutellarein significantly inhibited lung virus proliferation when administered intranasally or orally to mice. F36 and isoscutellarein showed negligible toxic effect against mice. These results suggested that flavones, which have potent influenza virus sialidase inhibitory activity, have anti-influenza virus activity in vivo.