The Sea Cucumber Thyonella gemmata Contains a Low Anticoagulant Sulfated Fucan with High Anti-SARS-CoV-2 Actions against Wild-Type and Delta Variants

In this work, we isolated two new sulfated glycans fromthe bodywall of the sea cucumber Thyonella gemmata: one fucosylatedchondroitin sulfate (TgFucCS) (17.5 +/- 3.5% kDa) and one sulfatedfucan (TgSF) (383.3 +/- 2.1% kDa). NMR results showed the TgFucCSbackbone composed of [-> 3)-beta-N-acetylgalactosamine-(1 -> 4)-beta-glucuronicacid-(1 ->] with 70% 4-sulfated and 30% 4,6-disulfated GalNAcunits and one-third of the GlcA units decorated at the C3 positionwith branching alpha-fucose (Fuc) units either 4-sulfated (65%)or 2,4-disulfated (35%) and the TgSF structure composed of a tetrasacchariderepeating unit of [-> 3)-alpha-Fuc2,4S-(1 -> 2)-alpha-Fuc4S-(1 -> 3)-alpha-Fuc2S-(1 -> 3)-alpha-Fuc2S-(1 ->]( n ). Inhibitory properties of TgFucCS and TgSFwere investigated using SARS-CoV-2 pseudovirus coated with S-proteinsof the wild-type (Wuhan-Hu-1) or the delta (B.1.617.2) strains andin four different anticoagulant assays, comparatively with unfractionatedheparin. Molecular binding to coagulation (co)-factors and S-proteinswas investigated by competitive surface plasmon resonance spectroscopy.Among the two sulfated glycans tested, TgSF showed significant anti-SARS-CoV-2activity against both strains together with low anticoagulant properties,indicating a good candidate for future studies in drug development.

Automated summary

Two new sulfated glycans, TgFucCS and TgSF, were isolated from the sea cucumber Thyonella gemmata. NMR results revealed the structures and compositions of TgFucCS and TgSF. The inhibitory properties of these sulfated glycans against SARS-CoV-2 were investigated, and TgSF showed significant antiviral activity and low anticoagulant properties, making it a potential candidate for drug development.