POLYANION INHIBITORS OF HUMAN-IMMUNODEFICIENCY-VIRUS AND OTHER VIRUSES .2. POLYMERIZED ANIONIC SURFACTANTS DERIVED FROM AMINO-ACIDS AND DIPEPTIDES

A series of new polyanions was synthesized via gamma-polymerization, i n aqueous micellar solution, of omega-unsaturated anionic surfactants whose polar head was derived from amino acids or dipeptides. The obtai ned polyanions were evaluated for their activity against human immunod eficiency virus (HIV-1, HIV-2) and various other RNA and DNA viruses. All the test compounds proved active against HIV-1 and HIV-2, their 50 % inhibitory concentration (IC50) being in the range of 0.04-7.5 mu g/ mL, while they were not toxic to the host cells (CEM-4 or MT-4) at con centrations up to 100 mu g/mL or higher. The HIV-inhibitory effect inc reased with the hydrophilic character of the amino acid moiety. The co mpounds were found to interact with both the viral envelope glycoprote in gp120 and the cellular CD4 receptor, thus blocking virus-cell bindi ng and virus-induced syncytium formation. These polyanions also proved active against human cytomegalovirus at about the same IC50 as for HI V. In addition, they were also active, albeit at somewhat higher IC50 values (0.8-20 mu g/mL), against other enveloped viruses such as respi ratory syncytial virus and arenaviruses (Junin and Tacaribe). At yet h igher IC50 values (greater than or equal to 20 mu g/mL), some of the c ompounds showed activity against influenza A virus. No activity was ob served with any of the compounds against vesicular stomatitis virus, S indbis virus, Semliki forest virus, influenza B, parainfluenza type 3, and the nonenveloped viruses Coxsackie type B4, polio type 1, and reo virus type 1.