EFFECT OF THE VIROSTATIC NORAKIN(R) (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 (H1N 1)] 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 t he control value without norakin. At higher concentrations (greater th an or equal to 10(-4) M), cytotoxic effects occurred. Neither hemolysi s nor hemagglutination were affected by norakin concentrations up to 1 0(-4) M. An in vitro fluorescence dequenching assay was used to study the viral fusion activity in the presence and absence of norakin. Fusi on between influenza viruses and virus receptor-containing liposomes w as 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 t he pH dependence of PR8 viral activities like hemolysis and fusion. We therefore suggest that norakin does not interact directly with the vi ral hemagglutinin, but inhibits viral infection through increase of th e internal pH in the prelysosomal compartment.