Antiviral Activity of a Sulphated Polysaccharide Extracted from the Marine Pseudomonas and Marine Plant Dinoflagellata against Human Immunodeficiency Viruses and other Enveloped Viruses

Abstract

A natural sulphated mucopolysaccharide (OKU40), extracted from a marine plant Dinoflagellata, and an artificial sulphated polysaccharide (OKU41), prepared from a marine Pseudomonas, displayed antiviral activities against several enveloped viruses. OKU40 and OKU41 were found to be homogenous in electrophoresis and sedimation velocity and had a molecular weight of 8.0 × 1065.0 × 105respectively. The sulphation rate of OKU40 and OKU41 was 8.9% and 5.4%, respectively. Each OKU40 and OKU41 inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2) and zidovudineresistant HIV-1 in MT-4 cells at similar concentrations to those of dextran sulphate (molecular weight: 5000) (50% inhibitory concentrations: 0.86-1.95 μg mL−1), whereas these compounds did not affect the growth and viability of mock-infected MT-4 cells at concentrations up to 500 μg mL−1. These compounds proved inhibitory not only to HIV-1 and HIV-2 but also to other enveloped viruses, i.e. herpes simplex virus type 1, influenza virus A and B, respiratory syncytial virus and measles virus. OKU40 and OKU41 suppressed syncytium formation induced by cocultivation of MOLT-4/IIIb and MOLT-4 cells at concentrations higher than 20 μg mL−1. Although OKU41 inhibited the binding of HIV-1 to the host cells and the binding of anti-gp120 monoclonal antibody to HIV-1 gp120, OKU40 did not inhibit these bindings, suggesting that the mechanism of anti-HIV activity of OKU40 and OKU41 may be primarily due to the inhibition of virus-cell fusion and viral adsorption to the host cells, respectively. Furthermore, these compounds did not inhibit to the blood coagulation process at a concentration that was significantly inhibitory to HIV replication. The compounds appear to have an interesting potential as virucidal agents.