Effect of two novel inhibitors of the human immunodeficiency virus protease on the maturation of the HIV gag and gag-pol polyproteins.
The ability of two novel synthetic compounds to inhibit the HIV protease-mediated processing of HIV-1 precursor polyproteins was investigated in an in vitro gag-protease mixed lysate assay system and in an assay using recombinant baculoviruses engineered to express the HIV-1 gag and pol genes in cultured insect cells. With the in vitro mixed lysate assay we have shown that both compounds at 1 microM can completely inhibit the HIV-1 and HIV-2 protease-mediated release of p24 from the HIV-1 gag precursor at pH 5.5 and pH 7.0. In the intracellular baculovirus system these compounds were shown to inhibit the protease-mediated maturation of gag and also the excision of the protease moiety from its precursor.
Overton
H A
HA
Department of Chemotherapy Biology, Roche Products Ltd., Welwyn Garden City, Herts, U.K.
McMillan
D J
DJ
Gridley
S J
SJ
Brenner
J
J
Redshaw
S
S
Mills
J S
JS
D000818:Animals; D002460:Cell Line; D015685:Fusion Proteins, gag-pol / Q000096:biosynthesis* / Q000235:genetics; D015683:Gene Products, gag / Q000096:biosynthesis* / Q000235:genetics; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D007304:Insect Viruses / Q000235:genetics; D007313:Insecta; D011480:Protease Inhibitors / Q000494:pharmacology*
D015685:Fusion Proteins, gag-pol; D015683:Gene Products, gag; D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors