Inhibitors of polyamine biosynthesis block human cytomegalovirus replication

The antivirial activities of the few compounds available that are effective in the clinical treatment of virus infections are directed against nucleic acid synthesis. Attention has been drawn recently to the need to develop new strategies, based on specific inhibitors of other biopolymers with essential functions in virus replication. Polyamines may prove suitable targets, as these aliphatic bases are found in all animal cells, where they seem to have essential roles in the synthesis and stabilization of macromolecules. Human diploid fibroblasts (MRC5 cells) infected with human cytomegalovirus (CMV) have elevated levels of polyamines, and the polyamine antimetabolite methylglyoxal bis(guanylhydrazone) (MGB G) has potent antiviral activity. The growth of human CMV is also blocked by alpha -difluoromethylornithine (DFMO), a highly specific inhibitor of the initiation of polyamine biosynthesis. Cytochemical studies show this inhibitory effect is directed against early events in the virus replication cycle.