CHARACTERIZATION OF 2 STRUCTURALLY NOVEL HIV-1 PROTEASE INHIBITORS IDENTIFIED BY RATIONAL SELECTION

The human immunodeficiency,virus (HIV-1), associated with the AIDS (ac quired immunodeficiency syndrome) epidemic, encodes an aspartyl protea se that is essential for polyprotein processing in the virus (Navia et al., 1989). It has been demonstrated that inactivation of the proteas e either catalytically or by an inhibitor prevents infectious virion f ormation (Kohl et al., 1988; Darke et al., 1989). The acquired knowled ge of key molecular interactions occurring between inhibitors and aspa rtyl proteases, as well as the structural similarities between HIV-1 p rotease and human renin was used to rationally select candidates for H IV-1 screening from the pool of analogs designed as renin inhibitors. A minimal number of chosen compounds were tested in an HIV-1 protease assay system. Two structurally novel peptides emerged as potent enzyma tic protease inhibitors. This study highlights the selection process a nd characterizes the antiviral properties of the two novel analogs.