ABSTRACT
It was shown that amiloride, orthovanade and uabain induced almost a two-fold decrease in the rate of incubation medium oxidation by the chick embryo fibroblasts due to the Na+/H+ exchange and inhibited by more than 95 per cent the influenza virus activity. The following mechanism for inhibition of the influenza virus multiplication in the cells under the effect of the above mentioned substances was proposed: suppression of the cellular Na+/H+ exchange responsible for the decrease in pH value in the virus-carrying endosomes----prevention of the decrease in the intraendosomal pH value to the critical level----blocking of the acid dependent process of the virus uncoating----inhibition of the influenza infection as a whole.
Subject(s)
Hydrogen/metabolism , Orthomyxoviridae/pathogenicity , Sodium/metabolism , Amiloride/pharmacology , Animals , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Cells, Cultured/microbiology , Chick Embryo , Depression, Chemical , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/microbiology , Hydrogen-Ion Concentration , Orthomyxoviridae/drug effects , Orthomyxoviridae/physiology , Ouabain/pharmacology , Rimantadine/pharmacology , Vanadates/pharmacology , Virus Replication/drug effects , Virus Replication/physiologyABSTRACT
Remantadine has been shown to induce a decrease in acidification rate of incubation medium by chick embryo fibroblasts, caused both by Na+/H+ exchange and diffusion of lactic acid, the final product of glycolysis. The degree of acidification rate decrease grew with increasing concentration and time of cell incubation with preparation. Possible implementation of the inhibitory effect of remantadine on acid-dependent process of influenza virus uncoating by decreasing cellular Na+/H+ exchange and glycolysis is discussed.
