INHIBITION OF REVERSE-TRANSCRIPTASE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND CHIMERIC ENZYMES OF HUMAN IMMUNODEFICIENCY VIRUSES TYPE-1 AND TYPE-2 BY 2 NOVEL NONNUCLEOSIDE INHIBITORS

We have studied the effects of two non-nucleoside reverse transcriptas e inhibitors (NNRTI), nitrophenyl phenyl sulfone (NPPS) and a potent d erivative of oxathiin carboxanilide (UC-38), on enzymatically active m olecular chimeras composed of complementary segments of the reverse tr anscriptases (RTs) of human immunodeficiency virus type 1 (HIV-1) and -2 (HIV-2). The substances inhibit only the DNA polymerase activity of HIV-I RT with no effect on HIV-2 RT. The results suggest that there i s a protein segment located between residues 158 and 190 that is criti cal for the inhibition by both compounds. However, there is probably a second segment that resides between residues 192 and 202, as in the c ase of NPPS, or residues 203 and 224, as in the case of UC-38, that is also crucial for the sensitivity of HIV-1 RT to both inhibitors.