Rapid Prescreening for Antiviral Agents against HIV-1 Based on Their Inhibitory Activity in Site-Directed Immunoassays. I. The V3 Loop of gp 120 as Target

Abstract

The anionic triphenylmethane derivative aurintricarboxylic acid (ATA) was reported to inhibit the replication and cytopathogenicity of human immunodeficiency virus type 1 (HIV-1). This antiviral effect, ascribed to the inhibitory activity of ATA on the virus reverse transcriptase, was subsequently also explained by binding of ATA to the HIV-1 envelope glycoprotein gp120 and/or to the CD4 receptor for the virus. Results presented here show: (1) the effectiveness of ATA as a potential antiviral drug by demonstrating that HIV-1 replication in vitro can be completely aborted in the presence of ATA as measured by the polymerase chain reaction; (2) that ATA inhibited the reaction between gp120 and antibodies specific for the V3 hypervariable loop of gp120; (3) that additional compounds with anti-HIV-1 activity can be rapidly identified based on their inhibitory effects measured by radioimmunoassays and/or enzyme-linked immunoadsorbent assays; and (4) that ATA also bound to synthetic peptides representing V3 loops of several HIV-1 isolates, suggesting the possibility that selected chemicals would interfere with the biological function of V3 loops of most HIV-1 isolates and would be effective for chemotherapy, and possibly for prophylaxis, of HIV-1 infections.