INHIBITORY EFFECTS OF NOVEL NUCLEOSIDE AND NUCLEOTIDE ANALOGS ON EPSTEIN-BARR-VIRUS REPLICATION

The anti-Epstein-Barr virus (EBV) activity of different classes of com pounds was assessed by means of an EBV DNA hybridization assay using a digoxigenin-labelled probe specific for the BamHI W fragment of the E BV genome, as well as by measuring viral capsid antigen (VCA) expressi on after a 7 day incubation period of P3HR-1 producer cells with the t est substances. Acyclovir, ganciclovir, cidofovir and zidovudine were included as reference compounds. Several compounds proved to be potent and selective inhibitors of EBV DNA synthesis and VCA expression. Of the new compounds that were evaluated for their anti-EBV activity, the highest efficacy (lowest EC,,) and highest selectivity index ISI) wer e shown by the purine nucleoside analogue 2-amino-7-[(1,3-dihydroxy-2- propoxy)methyl]purine (S2242) (EC50 0.6 ng/ml; SI 600), the acyclic nu cleoside phosphonate analogues 9-(2-phosphono-methoxyethyl)-6-dimethyl aminopurine (EC50 1.1 mu g/ml; SI 91), phonomethoxyethyl)-2-amino-6-be nzhydrylaminopurine (EC(50)1.3 mu g/ml; SI 29), 7-(2-phosphonomethoxye thyl)-6-dimethyl-aminopurine (EC50 0.8 mu g/ml; SI 56), omethoxypropyl )-6-(2-dimethylaminoethylaminopurine (EC50 0.5 mu g/ml; SI 42), the 2' ,3'-dideoxythymidine derivative 3'-oximino-2',3'-dideoxythymidine (EC5 0 1.5 mu g/ml; SI 65), and o-beta-D-threo-pentafuranyl)pentafuranosyl) thymine (EC50 4.1 mu g/ml; SI >24).