Significant anti-HIV activity of new modified polyanionic polymers in vitro

• Published in: Immunopharmacology and immunotoxicology Vol. 14; no. 4; p. 707
• Main Authors: Buckheit, Jr, R W, White, E L, Shannon, W M, Guerrero, A, Pivel, J P, Carrasco, L, Leal, J A, Chirigos, M A
• Format: Journal Article
• Language: English
• Published: England 1992
• Subjects: Anions - pharmacology; Antiviral Agents - pharmacology; Cell Line; DNA - biosynthesis; HIV-1 - drug effects; HIV-2 - drug effects; Humans; Polymers - pharmacology; Zidovudine - pharmacology
• ISSN: 0892-3973

The anti-HIV activities of two new polyanionic polymers (AM 242 and AM 612) were investigated in cell culture-based and biochemical antiviral assays. These compounds inhibited the reverse transcriptases from HIV-1 and HIV-2, using enzyme purified from virions and either a ribosomal RNA or gapped duplex DNA as the template. With the ribosomal RNA template, AM 242 and AM 612 had ID50 values of 1.1 and 0.10 micrograms/ml against the HIV-1 reverse transcriptase. In vitro cell based assays determined that both compounds significantly inhibited both the cytopathic effects associated with HIV-1 infection and the replication of virus in infected cells. AM 242 had an IC50 of approximately 1.0 micrograms/ml, while that of AM 612 was 0.19 micrograms/ml. These two active polyanionic polymers were effective in inhibiting the growth of a panel of HIV-1 isolates and were also active against HIV-2. Although the compounds were toxic at high concentration, they had antiviral activity over a wide range of nontoxic concentrations, yielding a high selectivity index. AM 612 was 100% protective for CEM cells from 320 ng/ml to 1 microgram/ml. Both compounds caused a significant increase in cellular proliferation as determined by the concentration-dependent increase in incorporation of radioactive precursors into cellular macromolecules.