The incidence of HIV positivity among IV drug abusers is substantially higher than that of the general population. As these patients progress to AIDS, they suffer extensive morbidity and mortality and mortality from herpesvirus infections. Unfortunately, only a limited selection of drugs are available to treat herpesvirus infections, and for some viruses (e.g., HCMV), effective therapy comes at the cost of dangerous toxicity that must be carefully monitored. Furthermore, because these drugs all act by inhibiting the viral DNA polymerase, the emergence of virus strains that are resistant to one and often several of these antiviral drugs has become a significant problem. In preliminary studies, remarkable effects of the halogenated benzimidazoles on genome packaging of guinea pig cytomegalovirus have been observed. The type of genomes that are formed, with respect to the presence of terminal repeats, is shifted to favor genomes with one repeat at the right end. At the left end, the genomes are truncated. Furthermore, these truncated genomes are packaged into capsids, but the capsids are permeable to nuclease. By learning how these drugs interfere with the cleavage/package process, the mechanisms of cleavage and packaging can be more clearly understood. From this basic knowledge may arise the means to design novel antiviral compounds that target the cleavage and packaging process. Such drugs will be clinical useful either alone or in combination therapies with the current polymerase inhibitors, in combating the wide range of serious manifestations of herpesvirus infections within the HIV/IV drug abuser patient population.
