Effect of combinations of difluoromethylornithine (DFMO) and 9[(1,3-dihydroxy-2-propoxy) methyl]guanine (DHPG) on human cytomegalovirus.

Both the nucleoside analog 9[(1,3-dihydroxy-2-propoxy)methyl]guanine (ganciclovir; DHPG) and the polyamine synthesis inhibitor difluoromethylornithine (DFMO) have been reported to inhibit replication of cytomegalovirus (CMV) in vitro. In these studies, DHPG inhibited human CMV replication at concentrations of 0.1 microM or greater, while DFMO was active (and then only inconsistently) at 5 mM or greater. (DFMO was added to cells 3 days before virus to maximize polyamine depletion.) However, DHPG combined with DFMO synergistically inhibited the replication of CMV strain AD169 and one wild-type CMV strain in human foreskin fibroblasts; the effect was evident on both virus yield and plaque formation. The synergistic effect of these two drugs on CMV replication could potentially be exploited clinically to limit drug toxicity or increase efficacy.