A synthetic, symmetry-based inhibitor of the human immunodeficiency virus type 1 (HIV-1) protease, A77003, was evaluated for antiviral activity and cytotoxicity in vitro in human peripheral blood lymphocytes or cell lines H9, CEM, and U937. Toxicity and antiviral activity of the HIV-1 protease inhibitor were compared with those of the reverse transcriptase inhibitors zidovudine and 2',3'-dideoxy-2',3'-didehydrothymidine and human recombinant alpha and beta interferons. Production of infectious virus particles, cell- free p24 antigen, and cell-associated viral proteins was reduced 50% by the HIV-1 protease inhibitor at concentrations of 0.12 to 0.26 μM (50% effective concentration [EC50]) in acute infection and 0.2 to 1.7 μM (EC50) in persistent infection. Fluorescence-activated cell sorter analysis of U937 cells persistently infected with HIV(IIIB) using a monoclonal antibody to HIV also showed a reduction of cell-associated viral protein in A77003-treated cells. Furthermore, toxicity of A77003 assessed by 3-[4,5-dimethylthiazol-2- yl]-2,5-diphenyltetrazolium bromide assay was not observed at greater than 100 times the EC50. A77003 was more effective in persistent HIV-1 infection than alpha and beta interferons (1,000 U/ml), while zidovudine and 2',3'- dideoxy-2',3'-didehydrothymidine were not active.
|Original language||English (US)|
|Number of pages||5|
|Journal||Antimicrobial Agents and Chemotherapy|
|State||Published - 1993|
ASJC Scopus subject areas
- Pharmacology (medical)