Although a number of
antiviral drugs inhibit replication of Epstein-Barr virus (EBV) in cell culture, and
acyclovir (ACV) suppresses replication in vivo, currently available drugs have not proven effective for treatment of EBV-associated diseases other than
oral hairy leukoplakia.
Benzimidazole riboside compounds represent a new class of
antiviral compounds that are potent inhibitors of human cytomegalovirus (HCMV) replication but not of other herpesviruses. Here we characterize the effects of two compounds in this class against lytic replication of EBV induced in a
Burkitt lymphoma cell line latently infected with EBV. We analyzed linear forms of EBV genomes, indicative of lytic replication, and episomal forms present in latently infected cells by terminal probe analysis followed by Southern blot hybridization as well as the high-molecular-weight unprocessed
viral DNA by pulsed-field gel electrophoresis. D-Ribofuranosyl
benzimidazole compounds that act as inhibitors of HCMV
DNA maturation, including BDCRB (5, 6-dichloro-2-bromo-1-beta-D-ribofuranosyl-1H-benzimidazole), did not affect the accumulation of high-molecular-weight or monomeric forms of EBV
DNA in the induced cells. In contrast, the generation of linear EBV
DNA as well as precursor
viral DNA was sensitive to the L-riboside
1263W94 [5, 6-dichloro-2-(isopropylamino)-1-beta-L-ribofuranosyl-1H-
benzimidazole]. The 50% inhibitory concentration range for
1263W94 was 0.15 to 1. 1 microM, compared with 10 microM for ACV. Thus,
1263W94 is a potent inhibitor of EBV. In addition,
1263W94 inhibited the phosphorylation and the accumulation of the essential EBV replicative cofactor, early
antigen D.