Kausik Chattopadhyay

Focus on antivirally active sulfated polysaccharides: From structure-activity analysis to clinical evaluation

In recent years, many compounds having potent antiviral activity in cell culture have been detected and some of these compounds are currently undergoing either preclinical or clinical evaluation. Among these antiviral substances, naturally occurring sulfated polysaccharides and those from synthetic origin are noteworthy. Recently, several controversies over the molecular structures of sulfated polysaccharides, viral glycoproteins, and cell-surface receptors have been resolved, and many aspects of their antiviral activity have been elucidated. It has become clear that the antiviral properties of sulfated polysaccharides are not only a simple function of their charge density and chain length but also their detailed structural features. The in vivo efficacy of these compounds mostly corresponds to their ability to inhibit the attachment of the virion to the host cell surface although in some cases virucidal activity plays an additional role. This review summarizes experimental evidence indicating that sulfated polysaccharides might become increasingly important in drug development for the prevention of sexually transmitted diseases in the near future.

Structural features and antiviral activity of sulphated fucans from the brown seaweed Cystoseira indica

Natural compounds offer interesting pharmacological perspectives for antiviral drug development. In this study, we have analysed sulphated-fucan-containing fractions isolated from the brown seaweed Cystoseira indica. The crude water extract (CiWE) and the main fraction (CiF3) obtained by anion exchange chromatography had potent antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) without cytotoxicity for Vero cell cultures. Furthermore, they had no direct inactivating effect on virions in a virucidal assay, and lacked anticoagulant activity. The mode of action of these compounds could be mainly ascribed to an inhibitory effect on virus adsorption. Chemical, chromatographic and spectroscopic methods showed that the major polysaccharide had an apparent molecular mass of 35 kDa and contained a backbone of α-(1→3)-linked fucopyranosyl residues substituted at C-2 with fucopyranosyl and xylopyranosyl residues. This sulphated fucan, considered the active principle of the C. indica water extract, also contained variously linked xylose and galactose units and glucuronic acid residues. Sulphate groups, if present, are located mostly at C-4 of (1→3)-linked fucopyranosyl units, and appeared to be very important for the anti-herpetic activity of this polymer.

Anti-herpetic activity of a sulfated xylomannan from Scinaia hatei

Many viruses display affinity for cell surface heparan sulfate proteoglycans with biological relevance in virus entry. This raises the possibility of the application of sulfated polysaccharides in antiviral therapy. In this study we have analyzed polysaccharide fractions isolated from Scinaia hatei. The crude water extract (ShWE) as well as one fraction (F1) obtained by size exclusion chromatography had potent anti-HSV activity. Their inhibitory concentration 50% (IC50) values ranging from 0.5 to 4.6 microg/ml were much lower than the cytotoxic concentration 50% (CC50) values (1000 microg/ml). These fractions had very low anticoagulant activity. Furthermore, they had a weak inactivating effect on virions in a virucidal assay at concentrations in the range of 60-100 microg/ml. Chemical, chromatographic and spectroscopic methods showed that the major polysaccharide, which had 0.4 sulfate group per monomer unit and an apparent molecular mass of 160 kDa, contained a backbone of alpha-(1-->3)-linked D-mannopyranosyl residues substituted at C-6, C-4 and C-2 with single stub of beta-d-xylopyranosyl residues. Sulfate groups, when present, are located at C-4 of alpha-(1-->3)-linked D-mannopyranosyl units, and appeared to be very important for the anti-herpetic activity of this polymer.

Polysaccharides from Gracilaria corticata: sulfation, chemical characterization and anti-HSV activities.

In this study, we have analyzed water-extracted polysaccharides of Gracilaria corticata. The water extract (WE), a galactan-containing sub-fraction (F3) and their hyper sulfated derivatives (WES1, WES2, F3S1 and F3S2) had anti-HSV activity with inhibitory concentration 50% (IC50) from 1.1 to 27.4 microg/ml. Sub-fraction F3, which has a molecular mass of 30 kDa, consists of a backbone of beta-(1-->3) and alpha-(1-->4)-linked-galactopyranosyl residues. This linear galactan contained Gal2Xyl1, Gal2AnGal2, Gal4 and Me-Gal3AnGal2 as oligomeric building subunits. Sulfate group was located at C-4 of (1-->3)-linked galactopyranosyl residues of the native galactan, and appeared to be very important for the anti-herpetic activity.

CONSTRUCTING BANASCHEWSKI COMPACTIFICATION WITHOUT DEDEKIND COMPLETENESS AXIOM

The main aim of this paper is to provide a construction of the Banaschewski compactification of a zero-dimensional Hausdorff topological space as a structure space of a ring of ordered field-valued continuous functions on the space, and thereby exhibit the independence of the construction from any completeness axiom for an ordered field. In the process of describing this construction we have generalized the classical versions of M. H. Stones theorem, the Banach-Stone theorem, and the Gelfand-Kolmogoroff theorem. The paper is concluded with a conjecture of a split in the class of all zero-dimensional but not strongly zero-dimensional Hausdorff topological spaces into three classes that are labeled by inequalities between three compactifications of X, namely, the Stone-Cech compactification βX, the Banaschewski compactification β0X, and the structure space 𝔐X,F of the lattice-ordered commutative ring ℭ(X,F) of all continuous functions on X taking values in the ordered field F, equipped with its order topology. Some open problems are also stated.