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A galactan sulfate (GS) was isolated from an aqueous extract of the red seaweed Aghardhiella tenera and partially purified. GS inhibited the cytopathic effect of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) in MT-4 cells at concentrations 10-fold higher than those required for the inhibition by dextran sulfate (MW 5000) of the cytopathic effect of HIV-1 and HIV-2 (50% inhibitory concentrations: 0.5 and 0.05 mu gml(-1), respectively). GS suppressed syncytium formation between MOLT-4 cells and persistently HIV-1- or HIV-2-infected HUT-78 cells at concentrations higher than 5 mu gml(-1). Like dextran sulfate (DS) and aurintricarboxylic acid (ATA), GS inhibited the binding of HIV-I to the cells and the binding of anti-gp120 mAb to HIV-1 gp120. Like DS and ATA, GS proved active not only against HIV-I and HIV-2 but also against other enveloped viruses, i.e. herpes-, toga-, arena-, myxo- and rhabdoviruses. GS represents a natural polysaccharide with broad-spectrum activity against a number of important viral pathogens. ispartof: Antivir Chem Chemoth vol:5 issue:5 pages:297-303 status: published

Polyanionic compounds [i.e. pentosan polysulphate, dextran sulphate, heparin, suramin, and aurintricarboxylic acid (ATA)] and castanospermine were examined for their inhibitory effect on human immunodeficiency virus (HIV) strains (HIV-1IIIB, HIV-1RF, HIV-2RODand HIV-2EHO) in two different assays (HIV cytopathicity in MT-4 cells and HIV antigen expression in CEM cells). In the MT-4 assay dextran sulphate and pentosan polysulphate were more active against HIV-2ROD, suramin was more active against HIV-1RF, and ATA more active against HIV-2EHO-Heparin was less, but castanospermine was more, active against the two HIV-2 strains. In the CEM assay dextran sulphate and suramin were equally active against all HIV strains, pentosan polysulphate was more active against both HIV-2 strains, whereas heparin was less active against HIV-2RODand ATA again was more active against HIV-2EHO. The compounds and soluble CD4 (sCD4) were also tested in the HIV-induced syncytium formation assay, where chronically infected HUT-78 cells were mixed with uninfected MOLT-4 or CEM cells. The inhibitory effect of suramin and ATA on syncytium formation was independent of the virus strain or cell type. For dextran sulphate and pentosan polysulphate, it was dependent on virus strain, and for heparin, castanospermine, and sCD4, it was dependent on both the virus strain and cell type.

The collaborative study was undertaken to examine the sensitivity of a range of tests used in assessing the antiviral activities of compounds against human immunodeficiency virus (HIV). A panel of 20 compounds with diverse antiviral activities against HIV were tested under code at three antiviral testing centres supported by the Medical Research Council's AIDS Directed Programme and at the European Community Centralised Facility (ECCF) for New Antiviral Compounds against AIDS in Belgium. Compounds known to have major anti-HIV activity ranked high in all assays, with the exception of the glucosidase inhibitors and certain nucleoside analogues. Results of two assays based on MT4 cells (centre IV) showed a high degree of similarity, despite the use of distinct HIV-1 (HTLV-IIIB) and HIV-2 (ROD) viruses. Considerable similarity was also observed between the assays based on HTLV-IIIRF in C8166 cells (centres I and II). Other assays performed at centre II and at centre III had enhanced sensitivity for glycosidase inhibitors. The differences in anti-HIV activity that were observed may be attributable to specific properties of the cell lines used and particular testing methodologies. The use of more than one type of assay is advisable in order not to miss compounds with low to moderate activity against HIV.

Dextran sulphate inhibits the replication of enveloped viruses (such as retro-, herpes-, toga, arena-, rhabdo-, orthomyxo- and paramyxoviruses), but is inactive against non-enveloped viruses (such as polio, Coxsackie and reovirus). Within the molecular weight (MW) range of 10000–50000, not much variation was observed in the antiviral potencies of different dextran sulphate (DS) samples, irrespective of the virus examined. However, in contrast with the higher MW samples, the low MW DS sample (prepared from dextran with a MW of 1000) was virtually inactive against herpes simplex virus type 1 and type 2, vesicular stomatitis virus, vaccinia virus, influenza A virus, respiratory syncytial virus and togaviruses (Sindbis, Semliki Forest). It was 10–20-fold less active than the higher MW samples against cytomegalovirus and arenaviruses (Junin, Tacaribe). The inhibitory potency of the 1000 MW DS sample against human immunodeficiency virus (HIV) varied considerably depending on the virus strain and cell type. When examined in MT-4 cells, the 1000 MW DS sample was 7000-, 1000-, 200- or 10-fold more inhibitory to HIV-1HE than HIV-2EHO, HTLV-IIIB, HTLV-IIIRF and LAV-2ROD, respectively. In CEM cells, however, HIV-1HE was less sensitive to the inhibitory effect of the 1000 MW DS sample than HIV-2EHO, equally sensitive as HTLV-IIIB and fivefold more sensitive than LAV-2ROD.