Effects of heteropolyanions and nucleoside analogues on rabies virus: In vitro study of syntheses and viral production

Abstract

Summary Among compounds previously shown to inhibit the production of rabies virus in vitro at doses which allowed normal cell multiplication, some showed dose-dependent inhibition while others showed 90% inhibition at all doses tested. The steps which, in rabies virus multiplication, were sensitive to inhibition by two heteropolyanions, tungstoantimoniate derivatives HPA-23 and 39, by a nucleoside analogue, virazole, and by one acyclic derivative of adenosine, (S)-DHPA, have been investigated in more detail. HPA-23 and 39 inhibited cellular protein synthesis and viral RNA synthesis; an accumulation of viral proteins inside the cell was observed and the G protein was found inserted in the plasma membrane. Virazole inhibited cell and viral RNA synthesis as well as viral protein synthesis; during infection, no G protein could be found in the plasma membrane although it remained present in the cytoplasm. (S)-DHPA did not affect cell synthesis (RNA and protein) or viral protein synthesis, but did inhibit the synthesis of viral RNA.