Despite recent developments in drug and compound design to combat the human immunodeficiency virus (HIV), there remains a need for a potent, nontoxic compound that is effective against wild type reverse transcriptase (RT), as well as RTs that have undergone mutations and thereby become refractory to commonly used anti-HIV compounds.
There are two major classes of RT inhibitors. The first comprises nucleoside analogues. Nucleoside analogues can cause serious side effects and have resulted in the emergence of drug-resistant viral strains that contain mutations in their RT. The second major class of RT inhibitors comprises non-nucleoside RT inhibitors (NNRTIs) that do not act as DNA chain terminators and are highly specific for HIV-RT. Christopher Michejda, Marshall Morningstar, and Thomas Roth of the National Cancer Institute have developed a novel class of NNRTIs (substituted benzimidazoles) effective in the inhibition of HIV-RT wild type as well as against variant HIV strains resistant to many non-nucleoside inhibitors. These NNRTIs are highly specific for HIV-1 RT and do not inhibit normal cellular polymerases, resulting in lower cytotoxicity and fewer side effects than the nucleoside analogues, such as AZT. This novel class of compounds could significantly improve the treatment of HIV by increasing compliance with therapy.
More info: Sally Hu, Ph.D., 301-435-5606, hus@mail.nih.gov
