Sulfated polysaccharides are well-known as potent inhibitors of HIV-1 and -2 replications in vitro. It has been demonstrated that sulfated homopolysaccharides are more potent than heteropolysaccharides, and the sulfate group is necessary for anti-HIV activity.34 The most interesting ones include heparin, dextran sulfate, dextrin sulfate, pentosan polysulfate, and mannan sulfate (Figure 11.2), which are responsible for the inhibition of virus-cell binding.35 These compounds are also effective against other enveloped viruses, such as HSV, and HCMV, which usually cause opportunistic infections in immunocompromised patients. The polysulfates have shown a differential inhibitory activity against different HIV strains, suggesting that the target molecules for polysulfates are not the same. Experiments with dextran sulfate have shown that the antiviral activity is enhanced by increasing the molecular weight and degree of sulfation. Moreover, Ca-SP at low concentration does not produce an enhancement of virus-induced syncytium, as is observed in dextran sulfate cultures. Ca-SP has a low anticoagulant activity and a longer half-life in the blood of mice, compared to sulfate dextran. Calcium molecule of Ca-SP was shown to be essential for the inhibition of the viral infection,36 however; calcium ion can be replaced by sodium or potassium ions preserving its antiviral activity against HSV-1 infection. While divalent or trivalent metal cations reduce its activity, it is noteworthy that substitution by Pb2+ ion increases the antiviral activity more than Mg2+ ion.

Despolymerization of sodium-spirulan with hydrogen peroxide reduce the antiviral activity as its molecular weight is decreased.37

Sulfated polysaccharides exert their anti-HIV activity by shielding off the positively charged amino acids in the V3 loop of the viral envelope glycoprotein gp120. The V3 loop is necessary for virus attachment to cell surface heparan sulfate, a primary binding site, before a more specific binding occurs to the CD4 receptor of CD4+ T-cells.38'35


Several polysaccharides isolated from extracelullar fractions of S. platensis have showed a broad-spectrum antiviral activity, characterized by a strong inhibition in vitro of human viruses such as: HCMV, HSV-1, HHV-6, and HIV-1. These extracellular extracts are composed of 41% of carbohydrates and 57% proteins. Fractionation of one of these extracts by ion exchange chromatography revealed that the antiviral activity was basically in the anionic polysaccharide (spirulan-like substances), but not in proteins fractions. A detailed study in HCMV showed that the spirulan-like substances inhibit HCMV by interfering with both the adsorption and penetration stages of the viral infection. The early inhibition in HCMV replication cycle is similar to the one observed with HSV-1, but it is different for HHV-6, which is inhibited by these substances after the infection step, indicating that there are difference in the mode of action between HCMV and HHV-6. In addition, a second inhibitory effect is observed latter, during intracellular steps of HCMV replication.

To explain these effects, it has been suggested that besides the antiviral activity displayed by negatively charged polysaccharides, which may initially bind to the virus itself or to cellular surfaces, more effective antiviral activity might result from the binding of the polysaccharides to cellular surfaces. Thereby, polysaccharides might interfere with viral entry, but also induce regulatory stimuli giving way to intracellular antiviral effects. One of these intracellular antiviral mechanisms could be IFN induction; however, it has been demonstrated that none of spirulan-like molecules induce significant levels of IFN-a, i.

Therefore, the intracellular anti-HCMV must be related to other mechanisms rather than to IFN activity.19 It has been proposed that it is unlikely that spirulan-like molecules could effectively penetrate into the cells. But by confocal laser scanning microscopic (CLSM) analysis, sodium-spirulan (Na-SP), a modified spirulan molecule in which the calcium ion was replaced by sodium, has demonstrated to be internalized in HSV-1 infected cells37; therefore they might interfere with the viral replication events.


Immulina is another polysaccharide isolated from S. platensis, which showed potent immunostimulatory activity and does not contain sulfur or calcium. This substance is structurally complex, with an estimated molecular weight above ten million Daltons, is highly water soluble and comprise between 0.5% and 2.0% of microalgal weight.39


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