Antiviral Properties of the HIV-1 Proteinase Inhibitor RO 31-8959

The peptide derivative Ro 31-8959 has been shown to be a potent inhibitor of HIV proteinase with an IC₅₀ of 2 × 10⁻⁹M, against HIV-1_RF in acutely infected lymphoblastoid cells. This inhibition was not overcome by increasing the infectious dose or by extending the culture time. Similar antiviral activity was also obtained against HIV-2, SIV and several AZT-resistant strains of HIV-1. The time of addition of the inhibitor could be delayed for 22 h without significant loss of activity, supporting its mode of action as taking place late in the replication cycle of HIV-1. Ro 31-8959 also showed activity against chronically infected cells.