Effect of the virostatic Norakin (triperiden) on influenza virus activities

The effect of the virostatic norakin on various in vitro activities of influenza viruses was studied. The infectivity of the [A/PR/8/34 (H1N1)] strain for MDCK (Madin Darby canine kidney) cells was reduced by a factor of 10 with 10(-7) M norakin. At 10(-5) M, it was below 1% of the control value without norakin. At higher concentrations (> or = 10(-4) M), cytotoxic effects occurred. Neither hemolysis nor hemagglutination were affected by norakin concentrations up to 10(-4) M. An in vitro fluorescence dequenching assay was used to study the viral fusion activity in the presence and absence of norakin. Fusion between influenza viruses and virus receptor-containing liposomes was not significantly affected up to norakin concentrations of 10(-3) M. However, the intracellular pH in MDCK cells was raised from pH 5.3 (without norakin) to about pH 6 with 10(-5) M norakin. This parallels the pH dependence of PR8 viral activities like hemolysis and fusion. We therefore suggest that norakin does not interact directly with the viral hemagglutinin, but inhibits viral infection through increase of the internal pH in the prelysosomal compartment.