INHIBITION OF ACTIVITY OF THE PROTEASE FROM BOVINE LEUKEMIA-VIRUS

In view of the close similarity between bovine leukemia virus (BLV) an d human T-cell leukemia virus type I (HTLV-I) we investigated the poss ibility of developing specific inhibitors of the proteases of these re troviruses using the purified enzyme from BLV. We tested the ability o f this protease to specifically cleave various short oligopeptide subs trates containing cleavage sites of BLV and HTLV-I proteases, as well as a recombinant BLV Gag precursor. The best substrate, a synthetic de capeptide bearing the natural cleavage site between the matrix and the capsid proteins of BLV Gag precursor polyprotein, was used to develop an inhibition assay. We determined the relative inhibitory effect of synthetic Gag precursor-like peptides in which the cleavable site was replaced by a non-hydrolyzable moiety. The encouraging inhibitory effe ct of these compounds indicates that potent non-peptidic inhibitors fo r retroviral proteases are not unattainable.