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.
Lin
J C
JC
Lineberger Cancer Research Center, School of Medicine, University of North Carolina Chapel Hill 27514.
DeClercq
E
E
Pagano
J S
JS
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000963:Antimetabolites; D000998:Antiviral Agents; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004279:DNA, Viral / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000187:drug effects* / Q000254:growth & development; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D014779:Virus Replication / Q000187:drug effects*
D000963:Antimetabolites; D000998:Antiviral Agents; D004279:DNA, Viral; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C016391:9-(2,3-dihydroxypropyl)adenine; C053001:adefovir; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D000225:Adenine; D000241:Adenosine