MECHANISM OF THE ANTIVIRAL ACTIVITY OF NEW AURINTRICARBOXYLIC ACID ANALOGS

Various new aurintricarboxylic acid (ATA) polymer analogues have been evaluated for their antiviral activity against a wide array of DNA and RNA viruses, and their mechanism of action against human cytomegalovi rus (HCMV) and human immunodeficiency virus type 1 (HIV-1). Most of th e polymers exhibited marked antiviral activity against a variety of en veloped viruses, but not against non-enveloped viruses, The ATA polyme rs displayed the most pronounced activity against HIV-1, HCMV and huma n herpesvirus type 6 (HHV-6), Their action against HCMV and HIV could be ascribed to inhibition of the initial attachment of virus particles to the cells, Using radiolabelled virus, we proved that the polymers inhibit the binding of HCMV to HEL fibroblasts, By flow cytometric ana lysis, we demonstrated that these new polymers interfere with (i) the binding of OKT4A monoclonal antibody (mAb) to the cellular CD4 recepto r, (ii) the binding of anti-gp120 mAb to HIV-1 glycoprotein (gp) 120, and (iii) the adsorption of HIV-1 virions and recombinant HIV-1gp120 ( rgp120) to MT-4 cells, The presence of a salicylic acid substituent on the central bridging carbon in the parent compound ATA seems to play an important role in the anti-HIV activity of these ATA related polyme r analogues.