Novel acyclic adenosine analogs inhibit Epstein-Barr virus replication

The effect of three new acyclic adenosine analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)adenine (PMEA), and (S)-9-(2,3-dihydroxypropyl)adenine [(S)-DHPA], on Epstein-Barr virus (EBV) replication was studied. Both (S)-HPMPA and PMEA but not (S)-DHPA effectively inhibited EBV DNA replication in virus-producer P3HR-1 cells and in latently infected Raji cells superinfected with P3HR-1 virus, as determined by cRNA-DNA hybridization and density gradient centrifugation. The 50% effective doses for inhibiting virus replication were 0.08 and 1.1 microM for (S)-HPMPA and PMEA, respectively. Both drugs were cytostatic but not cytotoxic to the cells at a concentration as high as 100 microM. These results indicate that (S)-HPMPA and PMEA are potent and selective anti-EBV agents in vitro.