Polyanions--a lost chance in the fight against HIV and other virus diseases?

Polyanions are known to exhibit potent antiviral activity in vitro, and may represent future therapeutic agents. This review summarizes literature reports, pertinent to anionic polymers as antiviral agents. The in vitro antiviral effects of numerous polyanionic compounds (sulphated polysaccharides, negatively charged serum albumin and milk proteins, synthetic sulphated polymers, polymerized anionic surfactants and polyphosphates) are described. This class of antiviral agent exhibits several unique properties that are not shared by other presently known antiviral agents: (i) a remarkable broad-spectrum antiviral activity against HIV-1, HIV-2 and a series of other enveloped viruses; (ii) the ability to inhibit syncytium formation between HIV-infected and normal CD4 T lymphocytes, a mechanism that drastically enhances HIV infectivity; and (iii) a low induction of viral drug-resistance. There is increasing evidence that polyanions interfere with the fusion process, a vital step in the viral replication cycle. The inhibition of virus-cell fusion appears to be the source of the antiviral activity of polyanions. In vivo, the pharmacological properties of polyanions result in a low bioavailability of the drugs to their viral targets, and hence a poor antiviral activity in vivo. It is suggested that polyanions must be used in combination with drug delivery systems in order to become therapeutically useful antiviral agents. Some drug delivery systems are briefly discussed.