Inhibition of vaccinia virus growth and virus-specific RNA synthesis by 3'-O-methyl adenosine and 3'-O-methyl guanosine.

The 5' triphosphates of the methylated nucleoside analogs 3'-O-methyl adenosine and 3'-O-methyl guanosine are RNA chain terminators in vitro. However, anticellular or antiviral effects of 3'-O-methylated nucleosides or nucleotides have not been investigated. This is presumably because of the assumption that cellular kinases will be unable to phosphorylate the nucleosides. We report here that contrary to this assumption, 3'-O-methyl adenosine and to a lesser extent 3'-O-methyl guanosine are potent inhibitors of vaccinia virus growth in L-cells and Vero cells, without having a significant effect on cell growth at concentrations required to inhibit virus growth. Experiments revealed that early virus-specific RNA synthesis was preferentially inhibited by both 3'-O-methyl adenosine and 3'-O-methyl guanosine.