New Polyacetal Polysulphate Active against Human Immunodeficiency Virus and other Enveloped Viruses

Abstract

A new polyacetal polysulphate, termed PAPS, was synthesized starting from dextran through oxidation, reduction, and subsequent sulphation. PAPS inhibited HIV-1- and HIV-2-induced cytopathicity in MT-4 cells at concentrations comparable to those required for dextran sulphate (MW5000) to inhibit the cytopathicity of these viruses (50% inhibitory concentration: 0.4–0.04 μg ml−1). At these concentrations PAPS had no anticoagulant activity. PAPS suppressed syncytium formation between MOLT-4 cells and persistently HIV-1- or HIV-2-infected HUT-78 cells at a concentration of 1 μg ml−1, that is 25- to 30-fold lower than that required for dextran sulphate to inhibit syncytium formation. Like dextran sulphate, PAPS inhibited HIV-1 binding to the cells and anti-gp120 mAb binding to HIV-1 gp120. Also, PAPS proved equally active as dextran sulphate against herpes simplex virus, cytomegalovirus and the arenaviruses Junin and Tacaribe, and 10-fold more active than dextran sulphate against vaccinia, Sindbis, influenza A, and vesicular stomatitis virus. Neither PAPS nor dextran sulphate proved inhibitory to the non-enveloped viruses polio, Coxsackie and reovirus. Pharmacokinetic studies in rabbits revealed that after intravenous bolus injection the serum concentrations of PAPS decayed biphasically, with an initial half-life of approximately 45–60 min. Twenty-four hours following their intraperitoneal administration to mice, PAPS as well as dextran sulphate generated low titres of an antiviral principle that was at least partially interferon-like.