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.