Structural insights and bioactivity of a cell wall sulfated polysaccharide from the marine diatom Cyclotella cryptica

Sulfated Polysaccharides (SPs) are abundant in marine organisms, where they play an essential role in the mechanisms of adaptation to saline environments. SPs from macro- and microalgae possess unique structural features, which often correlate to taxonomy, and are under active investigation due to their various potential fields of application. We have investigated the structure of the sulfated polysaccharide isolated from the cell wall of the marine diatom Cyclotella cryptica (CcSP), finding that it consisted of a homopolysaccharide with a backbone of (1 → 4)-⍺-d-Manp carrying, in the most abundant form, sulfation at O-6. CcSP exhibited promising antiviral activity against Herpes Simplex Virus-1 (HSV-1), which was likely associated with a mechanism involving steric hindrance and/or electrostatic repulsion, preventing viral attachment to host cells. In addition, we have also proved the binding of CcSP to the innate human receptor Langerin, a well-known C-type lectin that recognizes sulfated polysaccharides and is involved in virus entry in cells. We attempted to partially reconstruct the biosynthetic pathway of CcSP: analysis of C. cryptica genome revealed the presence of several putative carbohydrate 6-O sulfotransferases (CH-STs) with homology to the human enzymes involved in glycosaminoglycans sulfation. Our results suggest an ancient evolutionary origin for the regioselective specialization of CH-STs, and could pave the way for future research on diatom cell wall biogenesis, as well as for biotechnological applications relying on the manipulation of the sulfation levels in CcSP for enhanced activity.