1. Academic Validation
  2. Activity of the anti-HIV agent 9-(2-phosphonyl-methoxyethyl)-2,6-diaminopurine against cytomegalovirus in vitro and in vivo

Activity of the anti-HIV agent 9-(2-phosphonyl-methoxyethyl)-2,6-diaminopurine against cytomegalovirus in vitro and in vivo

  • Eur J Clin Microbiol Infect Dis. 1993 Jun;12(6):437-46. doi: 10.1007/BF01967438.
J Neyts 1 F Stals C Bruggeman E De Clercq
Affiliations

Affiliation

  • 1 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Abstract

9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP), a potent inhibitor of human immunodeficiency virus (HIV) replication, was evaluated for its activity against human cytomegalovirus (HCMV) in vitro, and murine cytomegalovirus (MCMV) and rat CMV (RCMV) in vivo. PMEDAP strongly inhibited HCMV-induced cytopathicity in human embryonic lung (HEL) cell cultures (EC50 11 microM) and caused a concentration-dependent suppression of viral DNA synthesis (IC50 20 microM) [corrected]. PMEDAP had no effect on the expression of HCMV-specific immediate early antigens (IEA) as measured on day 1 post-infection, but inhibited the expression of HCMV late antigens as measured on day 6 post-infection (EC50 20 microM) [corrected]. The diphosphate derivative of PMEDAP (PMEDAPpp) selectively inhibited HCMV-induced DNA Polymerase (IC50 0.1 microM). PMEDAP proved markedly effective in reducing the mortality rate of NMRI mice that had been infected intraperitoneally or intracerebrally with a lethal dose of MCMV. PMEDAP exhibited greater anti-MCMV activity when administered as a single dose immediately after Infection than when this dose was divided over repeated administrations. 9-(2-phosphonylmethoxyethyl)-adenine (PMEA) also prevented MCMV-induced mortality, but only at a dose ten-fold higher than that of PMEDAP. PMEDAP also delayed death in severe combined immune deficiency (SCID) mice that had been infected with MCMV. The effect of PMEDAP on RCMV infections in rats was less pronounced.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-106382
    ≥98.0%, HIV Replication Inhibitor
    HIV; CMV