Effect of Pokeweed Antiviral Protein in Combination with Guanidine on Poliovirus Macromolecular Synthesis

Abstract

Viral RNA synthesis, total protein synthesis and the synthesis of specific poliovirus proteins were determined in the presence of synergistic (low) and antagonistic (high) combinations of PAP and guanidine. Viral proteins 3AB and 3C were blocked in the presence of either guanidine or PAP at low concentration. In the presence of the synergistic drug combination, proteins 2C, 2A and 3A, in addition to proteins 3AB and 3C failed to appear. Also, proteins 3D, VPO and VP3 were present in reduced amount. The mechanism of action of the synergistic drug combination may involve an inhibition in the processing of poliovirus polyprotein P1 which is the precursor protein for essential capsid endproducts VPO and VP3. Viral RNA synthesis was stimulated in the presence of either PAP or guanidine alone at low concentration and in the presence of the synergistic drug combination. This may be due to the absence of protein VPg (3B) which has a regulatory function on RNA synthesis. In contrast, viral RNA synthesis was inhibited almost completely in the presence of either PAP or guanidine at high concentration and in the presence of the antagon~sticd rug combination. The antagonistic drug combination resulted in the failure to synthesize plus-strand RNA from the parental RF-RNA which led to a complete absence of viral protein synthesis.