Antiviral properties of Ro 31-8959, an inhibitor of human immunodeficiency virus (HIV) proteinase.
Ro 31-8959 inhibits the spread of HIV infection and the production of cytopathic effects in cultures of acutely infected cells. IC50 values for these effects are in the range 0.5-6.0 nM and IC90 values are in the range 6.0-30.0 nM. This inhibitor is effective even when added to cultures at a late stage of infection, after syncytia have started to form. Virus antigen, virus particles and virus cytopathic effects can largely be cleared from cultures treated with compound from 3 days until 6 days post infection. In chronically-infected cells, inhibition of virus maturation can be detected after 24 hours' treatment with 10 nM Ro 31-8959. In addition, a significant reduction of the proteolytic processing of p56 to p24 can be demonstrated in these cells with compound at picomolar concentrations. These properties indicate that Ro 31-8959 is highly effective against HIV with the potential to inhibit acute, established acute and chronic infections.
Craig
J C
JC
Roche Products Ltd., Welwyn Garden City, Herts, U.K.
Duncan
I B
IB
Hockley
D
D
Grief
C
C
Roberts
N A
NA
Mills
J S
JS
D000998:Antiviral Agents / Q000494:pharmacology*; D002459:Cell Fusion / Q000187:drug effects; D002478:Cells, Cultured; D015488:HIV Antigens / Q000032:analysis; D015658:HIV Infections / Q000188:drug therapy*; D016333:HIV Protease / Q000494:pharmacology; D017320:HIV Protease Inhibitors; D006801:Humans; D066298:In Vitro Techniques; D019258:Saquinavir; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D016333:HIV Protease; D019258:Saquinavir