BIOCHEMICAL BASIS FOR INCREASED SUSCEPTIBILITY TO CIDOFOVIR OF HERPES-SIMPLEX VIRUSES WITH ALTERED OR DEFICIENT THYMIDINE KINASE-ACTIVITY

It has been observed that herpes simplex virus mutants with deficient or altered thymidine kinase activity are more susceptible to Cidofovir {CDV; 1-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl] cytosine dihydrate} in tissue culture than are the parental strains. During infection of cells, the elevation of the dCTP pool by thymidine kinase mutant viruses is less than that induced by the wild-type virus. The competition between CDV diphosphate and dCTP at the viral polymerase is therefore changed in favor of CDV diphosphate, enhancing its activity.