Viral Inhibition Studies on Sulfated Lignin, a Chemically Modified Biopolymer and a Potential Mimic of Heparan Sulfate

Abstract

In our previous work, we discovered potent HSV-1 inhibitory activity arising from sulfated form of lignin, a highly networked natural biopolymer composed of substituted phenylpropanoid monomers (Raghuraman et al. Biomacromolecules 2005, 6, 2822). We present here detailed characterization of the viral inhibitory properties of this interesting macromolecule. The inhibition was proportional to the average molecular weight of the lignin sulfate preparation with IC₅₀ values in the range of 17 nM to 5 μM against HSV-1 and HSV-2, and 29 nM to 763 nM against HIV-1. Cytotoxicity studies displayed selectivity indices in the range of 14 to 31 suggesting reasonably good difference between activity and toxicity for polymeric preparations. Comparative molecular modeling studies suggest that lignin sulfate may contain certain structural features that mimic the three-dimensional organization of sulfate groups in heparan sulfate, thereby providing a plausible basis for its anti-viral activity. The combination of strongly hydrophobic (–Ar) and strongly hydrophilic (–OSO₃⁻) groups in lignin sulfate makes this chemically modified biopolymer an interesting molecule for further work.