Rapid Prescreening for Antiviral Agents against HIV-1 Based on Their Inhibitory Activity in Site-Directed Immunoassays. Approaches Applicable to Epidemic HIV-1 Strains

Abstract

Several compounds, including the triphenylmethane derivative aurintricarboxylic acid (ATA) and porphyrins, were reported to inhibit the binding of anti-V3 loop-specific antibodies to the V3 loop of gp120 from HIV-1 III-B and to have antiviral activity, probably due to interference with the biological function of the V3 loop. However, these compounds can be applied to antiviral chemotherapy only if they interact with envelope glycoproteins from a multitude of epidemic HIV-1 strains and inhibit their replication. Since recombinant envelope glycoproteins, synthetic peptides and anti-V3 monoclonal antibodies may not be available for these HIV-1 strains, alternative assays are needed to prescreen different compounds for potential antiviral activity against these viruses. Results presented here indicate that: (1) virions of HIV-1 MN, most closely related to primary HIV-1 isolates from European and North American countries, and human anti-HIV-1 antibodies, can also be used for rapid prescreening of antiviral agents, (2) compounds with antiviral activity against HIV-1 MN, discerned by site-directed immunoassays, inhibited the reaction of human anti-HIV-1 with a V3 loop consensus peptide corresponding to European/North American HIV-1 isolates, and (3) meso-tetra (4-carboxyphenyl) porphine (MTCPP), one of the most potent inhibitors of HIV-1 replication selected on the basis of site-directed immunoassays, preferentially attached to the V3 loop of gp120.