Anti-HIV-1 activity of low molecular weight sulfated chitooligosaccharides

Chitooligosaccharides are nontoxic and water-soluble compounds obtained by enzymatic degradation of chitosan, which is derived from chitin by a deacetylation process. Chitooligosaccharides possess broad range of activities such as antitumour, antifungal, antibacterial activities. Sulfated chitooligosaccharides (SCOSs) with different molecular weights were synthesized by a random sulfation reaction. In the present study, anti-HIV-1 properties of SCOSs and the impact of molecular weight on their inhibitory activity were investigated. SCOS III (MW 3–5 kDa) was found to be the most effective compound to inhibit HIV-1 replication. At nontoxic concentrations, SCOS III exhibited remarkable inhibitory activities on HIV-1-induced syncytia formation (EC50 2.19 μg/ml), lytic effect (EC50 1.43 μg/ml), and p24 antigen production (EC50 4.33 μg/ml and 7.76 μg/ml for HIV-1RF and HIV-1Ba-L, respectively). In contrast, unsulfated chitooligosaccharides showed no activity against HIV-1. Furthermore, it was found that SCOS III blocked viral entry and virus-cell fusion probably via disrupting the binding of HIV-1 gp120 to CD4 cell surface receptor. These results suggest that sulfated chitooligosaccharides represent novel candidates for the development of anti-HIV-1 agent.

Graphical abstractSulfated chitooligosaccharides (SCOSs) were obtained in over 90% yield as white, fluffy, water-soluble compounds. Characteristic absorptions derived from sulfo groups in the IR spectrum at 800, 1240, and 1350 cm−1 were assigned to C–O–S, S=O, and S–N, respectively. In the present, anti-HIV-1 properties of SCOSs and the effect of their molecular weight on the inhibition of HIV-1 were investigated.Figure optionsDownload full-size imageDownload as PowerPoint slide