Prospects for the Use of Marine Sulfated Fucose-Rich Polysaccharides in Treatment and Prevention of COVID-19 and Post-COVID-19 Syndrome.

Symptoms of the new coronavirus infection that appeared in 2019 (COVID-19) range from low fever and fatigue to acute pneumonia and multiple organ failure. The clinical picture of COVID-19 is heterogeneous and involves most physiological systems; therefore, drugs with a wide spectrum of mechanism of action are required. The choice of the treatment strategy for post-COVID-19 syndrome is still a challenge to be resolved. Polysaccharides with a high fucose content derived from seaweed and marine animals can form the basis for the subsequent development of promising agents for the treatment of COVID-19 and post-COVID-19 syndrome. This class of biopolymers is characterized by a variety of biological activities, including antiviral, antithrombotic, anticoagulant, hemo-stimulating, anti-inflammatory and immune-regulatory. Low molecular weight derivatives of these polysaccharides, as well as synthetic oligosaccharides with a sufficient amount and sulfation type may be considered as the most promising compounds due to their better bioavailability, which undoubtedly increases their therapeutic potential.

Erratum to: Prospects for the Use of Marine Sulfated Fucose-Rich Polysaccharides in Treatment and Prevention of COVID-19 and Post-COVID-19 Syndrome.

[This corrects the article DOI: 10.1134/S1068162022060152.].

Influence of fucoidans and their derivatives on antitumor and phagocytic activity of human blood leucocytes.

The immunotropic activity of structurally different fucoidans and their derivatives towards isolated immune blood cells, effectors of innate immune system, was studied. The most potent effect was observed for high molecular weight fucoidan CF from the alga Chordaria flagelliformis, whose backbone is built of (1→3)-linked units of α-L-fucopyranose, and branches included residues of α-D-glucuronic acid and α-L-fucofuranose. This compound at the concentration of 0.05 mg/ml potentiated phagocytosis of Saccharomyces cerevisiae and Lactobacillus acidophilus by neutrophils, increasing relative quantity of phagocytes as well as their effectiveness. Along with this, 14% increase in the concentration of membrane-bound integrin CD11c molecules was observed. The systemic effect of CF at the dose of 0.01 mg/mouse i.p. led to potentiation of cytotoxic activity of spleen mononuclear leucocytes towards melanoma cells of line B16 by 1.9-fold and towards chronic myelogenous leukemia cells of line K-562 by 1.7-fold. These results indicate that fucoidan CF can stimulate anti-infective and antitumor activity of effectors of the innate immune system via CD11c integrins.

[Anticoagulant activity of fucoidans from brown algae].

The anticoagulant activity of polysaccharide fucoidans from 11 species of brown algae was studied. The anticoagulant activity was measured by the activated partial thromboplastin time (APTT), prothrombin time and thrombin time. Inhibitory action of fucoidans varied significantly from one species to another. Fucoidans from Laminaria saccharina and Fucus distichus showed high anticoagulant activities, while fucoidans from Cladosiphon okamuranus and Analipus japonicus were almost inactive. The fucoidan inhibitory effect on thrombin and factor Xa in the presence or in the absence of natural thrombin inhibitor, antithrombin III (AT III), was also studied. In contrast to the best studied anticoagulant heparin the most of the fucoidans inhibited thrombin in the absence of AT III. In the presence of AT III inhibitory effect of fucoidans was increased considerably. Unlike heparin, the effect of fucoidans on factor Xa was very weak in the presence of AT III and was not observed in the absence of AT III. The correlation between the anticoagulant activities of this series of fucoidans and their anti-inflammatory action, studied by us earlier, was not found. It is expected that two these types of fucoidan activities depend on different structural features of fucoidans. These findings show the possibility to obtain fucoidans with high anti-inflammatory action and with low anticoagulant activity. Anticoagulant activity of the fucoidans did not depend on the content of fucose, the other neutral sugars and sulfates in the preparations, and also on the structure of the backbone of molecule. Taken together, these results indicate on prospects of fucoidan study as potential therapeutic agents.

[Polysaccharides of algae: 60. Fucoidan from the Pacific brown alga Analipus japonicus (Harv.) Winne (Ectocarpales, Scytosiphonaceae)].

A fucoidan containing L-fucose, sulfate, and O-acetyl groups at a molar ratio of 3 : 2 : 1, as well as minor amounts of xylose, galactose, and uronic acids was isolated from the brown alga Analipus japonicus collected in the Sea of Japan. The structures of the native polysaccharide and the products of its desulfation and deacetylation were studied by the methods of methylation, periodate oxidation, and NMR spectroscopy. It was shown that the polysaccharide molecule mainly consists of a linear carbohydrate chain of (1-->3)-linked alpha-L-fucopyranose residues, which bear numerous branches in the form of single alpha-L-fucopyranose residues (three branches at position 4 and one branch at position 2 per each ten residues of the main chain). Sulfate groups occupy positions 2 and (to a lesser extent) 4, most of the terminal nonreducing fucose residues being sulfated twice. The acetyl groups are located predominantly at positions 4. The structural role of minor monosaccharides was not established.

Effect of enzyme preparation from the marine mollusk Littorina kurila on fucoidan from the brown alga Fucus distichus.

A fucoidanase preparation from the marine mollusk Littorina kurila cleaved some glycosidic bonds in fucoidan from the brown alga Fucus distichus, but neither fucose nor lower oligosaccharides were produced. The main product isolated from the incubation mixture was a polysaccharide built up of disaccharide repeating units -->3)-alpha-L-Fucp-(2,4-di-SO3(-))-(1-->4)-alpha-L-Fucp-(2SO3(-))-(1-->, the structure coinciding with the idealized formula proposed for the initial substance. A polymer fraction with the same carbohydrate chain but sulfated only at positions 2 and nonstoichiometrically acetylated at positions 3 and 4 of fucose residues was isolated as a minor component. It is suggested that the native polysaccharide should contain small amounts of non-sulfated and non-acetylated fucose residues, and only their glycosidic bonds are cleaved by the enzyme. The enzymatic hydrolysis showed that irregular regions of the native polysaccharide containing acetylated and partially sulfated repeating units were assembled in blocks.

[Polysaccharides of calcareous algae and their effect on calcification process]. / Polisakharidy izvestkovykh vodoroslei i ikh vliianie na prptsess kal'tsifikatsii.

The composition and structure of polysaccharides from several groups of calcareous algae (including calcareous cyanobacteria), which differ in the calcification mode (extracellular, cell wall, or intracellular), are reviewed. Two families of marine algae, Corallinaceae (Rhodophyta) and Cocolithophoraceae (Prymnesiophyta = Haptophyta), are considered in detail; they exhibit the cell wall and intracellular calcification modes, respectively, and synthesize unusual polysaccharides that seem to directly participate in the calcification process.

Structure of a sulfated xylogalactan from the calcareous red alga Corallina pilulifera P. et R. (Rhodophyta, Corallinaceae).

The structure of a sulfated polysaccharide isolated from the calcareous red alga Corallina pilulifera was studied by methylation analysis before and after desulfation or Smith degradation, as well as by 1D and 2D 1H and 13C NMR spectroscopy. The polysaccharide was shown to consist of D-galactose, L-galactose, 2-O-methyl-L-galactose, 3-O-methyl-L-galactose, 6-O-methyl-D-galactose, D-xylose, and sulfate in a molar ratio of 29:20:5:2:1:20:23. Its agaran-like backbone built up of alternating 3-linked beta-D-galactopyranose and 4-linked alpha-L-galactopyranose residues bears single beta-D-xylopyranosyl substituents at position 6 of beta-D-galactose residues, whereas sulfate and O-methyl groups occupy positions 2 and 3 of alpha-L-galactose and position 6 of beta-D-galactose residues.