Abstract
The halogenated benzimidazole derivative 5,6-dichloro-1-β- d-ribofuranosylbenzimidazole (DRB) inhibits reversibly the replication of human adenovirus type 2 (Ad2) and its DNA in human KB cells. Viral DNA replication is almost completely blocked when the drug is added earlier than 4 hr postinfection in concentrations between 50 and 150 μM. Replication of viral DNA in all four size-classes (>100 S, 50–90 S, 34 S, and <20 S) is inhibited. The replication block is reversible upon withdrawal of the inhibitor. When DRB is administered at the time of maximal viral DNA replication, 16–18 hr postinfection, the inhibitor has no apparent effect on viral DNA synthesis. In the presence of 150 μM DRB, synthesis of early virus-specific RNA in the nucleus is reduced by approximately 90% and the appearance of virus-specific RNA sequences in the cytoplasm is reduced by >95%, as demonstrated by DNA-RNA filter hybridization. Thus, the block in viral DNA replication is best explained by the inhibition of the synthesis of early virus-specific RNA.
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