ACTIVITY OF THE ANTI-HIV AGENT 9-(2-PHOSPHONYL-METHOXYETHYL)-2,6-DIAMINOPURINE AGAINST CYTOMEGALOVIRUS IN-VITRO AND IN-VIVO

9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), a potent inhi bitor of human immunodeficiency virus (HIV) replication, was evaluated for its activity against human cytomegalovirus (HCMV) in vitro, and m urine cytomegalovirus (MCMV) and rat CMV (RCMV) in vivo. PMEDAP strong ly inhibited HCMV-induced cytopathicity in human embryonic lung (HEL) cell cultures (EC50 3.1 muM) and caused a concentration-dependent supp ression of viral DNA synthesis (IC50 5.6 muM). PMEDAP had no effect on the expression of HCMV-specific immediate early antigens (IEA) as mea sured on day 1 post-infection, but inhibited the expression of HCMV la te antigens as measured on day 6 post-infection (EC50 5.8 muM). The di phosphate derivative of PMEDAP (PMEDAPpp) selectively inhibited HCMV-i nduced DNA polymerase (IC50 0.1 muM). PMEDAP proved markedly effective in reducing the mortality rate of NMRI mice that had been infected in traperitoneally or intracerebrally with a lethal dose of MCMV. PMEDAP exhibited greater anti-MCMV activity when administered as a single dos e immediately after infection than when this dose was divided over rep eated administrations. 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) als o prevented MCMV-induced mortality, but only at a dose ten-fold higher than that of PMEDAP. PMEDAP also delayed death in severe combined imm une deficiency (SCID) mice that had been infected with MCMV. The effec t of PMEDAP on RCMV infections in rats was less pronounced.