Development of a Novel Screen for Protease Inhibitors

We have developed a novel plasmid-based, quantitative, in vitro screen to test the protease-inhibiting activities of existing and newly discovered agents. Since the onset of the AIDS epidemic, a number of antiret-roviral drugs have been developed for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. While the initial target for therapy was the viral reverse transcriptase, inhibitors targeting the viral protease (PR) enzyme have be-come a mainstay of antiretroviral therapy. Although use of these compounds in multidrug regimens has dramatically re-duced viral load as well as morbidity and mortality, their long-term benefit in HIV-1-infected patients has been limited by the emergence of drug-resistant viral strains. The high rate of mutation of HIV-1 coupled with incomplete viral suppression and widespread use of this class of drugs will continue to contribute to this problem. For this reason, it is essential tha