Inhibitory Effects of Heterogeneous Dextran Sulphate Compounds on Simian Type D Retrovirus in vitro

Abstract

Nine heterogeneous dextran sulphate compounds were tested in vitro for their ability to inhibit a type D simian retrovirus (SRV-2) known to cause simian acquired immunodeficiency syndrome (SAIDS). Dextran sulphate, a sulphated polysaccharide, is available commercially in a variety of molecular weights ranging from 5000 (5K) to 500000 (500K). Of the four 500K compounds tested, three completely blocked replication and infectivity of SRV-2. Of the remaining five compounds tested, only three completely inhibited the virus. Cytotoxic effects also varied even among compounds of the same mol. wt. All nine compounds were further tested in combination with azidothymidine (AZT) or dideoxycytidine (ddC) for possible additive, synergistic or antagonistic effects at reduced concentrations of both drugs. Six dextran sulphate compounds showed slight additive or synergistic effects with AZT, while no effects were seen with ddC. The results suggest that the antiretroviral activity of dextran sulphate depends on the particular chemical preparation of the compound and is not entirely dependent on mol. wt. Thus, it is important to be aware of the inhibitory and cytotoxic variability in heterogeneous dextran sulphate compounds when considering the potential use of this drug, either alone or in combination, as an antiretroviral agent in vivo.