Marine sulfated glycans inhibit the interaction of heparin with S-protein of SARS-CoV-2 Omicron XBB variant.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide COVID-19 pandemic, leading to 6.8 million deaths. Numerous variants have emerged since its outbreak, resulting in its significantly enhanced ability to spread among humans.

Nuclear magnetic resonance-based structural elucidation of novel marine glycans and derived oligosaccharides.

Marine glycans of defined structures are unique representatives among all kinds of structurally complex glycans endowed with important biological actions. Besides their unique biological properties, these marine sugars also enable advanced structure-activity relationship (SAR) studies given their distinct and defined structures. However, the natural high molecular weights (MWs) of these marine polysaccharides, sometimes even bigger than 100 kDa, pose a problem in many biophysical and analytical studies.

The Sea Cucumber 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 from the body wall of the sea cucumber : one fucosylated chondroitin sulfate (TgFucCS) (17.5 ± 3.5% kDa) and one sulfated fucan (TgSF) (383.

SPR Sensor-Based Analysis of the Inhibition of Marine Sulfated Glycans on Interactions between Monkeypox Virus Proteins and Glycosaminoglycans.

Sulfated glycans from marine organisms are excellent sources of naturally occurring glycosaminoglycan (GAG) mimetics that demonstrate therapeutic activities, such as antiviral/microbial infection, anticoagulant, anticancer, and anti-inflammation activities. Many viruses use the heparan sulfate (HS) GAG on the surface of host cells as co-receptors for attachment and initiating cell entry. Therefore, virion-HS interactions have been targeted to develop broad-spectrum antiviral therapeutics.

Structural requirements of Holothuria floridana fucosylated chondroitin sulfate oligosaccharides in anti-SARS-CoV-2 and anticoagulant activities.

Fucosylated chondroitin sulfate (FucCS) is a unique glycosaminoglycan found primarily in sea cucumbers. This marine sulfated glycan is composed of a chondroitin sulfate backbone decorated with fucosyl branches attached to the glucuronic acid. FucCS exhibits potential biological actions including inhibition of blood clotting and severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection.

Inhibition of Cytomegalovirus by Fucosylated Chondroitin Sulfate Depends on Its Molecular Weight.

Many viruses attach to host cells by first interacting with cell surface proteoglycans containing heparan sulfate (HS) glycosaminoglycan chains and then by engaging with specific receptor, resulting in virus entry. In this project, HS-virus interactions were targeted by a new fucosylated chondroitin sulfate from the sea cucumber (PpFucCS) in order to block human cytomegalovirus (HCMV) entry into cells. Human foreskin fibroblasts were infected with HCMV in the presence of PpFucCS and its low molecular weight (LMW) fractions and the virus yield at five days post-infection was assessed.

Antiviral activity of marine sulfated glycans against pathogenic human coronaviruses.

Great interest exists towards the discovery and development of broad-spectrum antivirals. This occurs due to the frequent emergence of new viruses which can also eventually lead to pandemics. A reasonable and efficient strategy to develop new broad-spectrum antivirals relies on targeting a common molecular player of various viruses.

Anti-SARS-CoV-2 and anticoagulant properties of Pentacta pygmaea fucosylated chondroitin sulfate depend on high molecular weight structures.

Fucosylated chondroitin sulfate (FucCS) is a unique marine glycosaminoglycan that exhibits diverse biological functions, including antiviral and anticoagulant activity. In previous work, the FucCS derived from Pentacta pygmaea (PpFucCS) showed moderate anticoagulant effect but high inhibitory activity against the Wuhan strain of severe acute respiratory syndrome coronavirus (SARS-CoV-2). In this study, we perform free-radical depolymerization of PpFucCS by the copper-based Fenton method to generate low molecular weight (MW) oligosaccharides.

Inhibition of SARS-CoV-2 wild-type (Wuhan-Hu-1) and Delta (B.1.617.2) strains by marine sulfated glycans.

The Coronavirus disease pandemic has steered the global therapeutic research efforts toward the discovery of potential anti-severe acute respiratory syndrome coronavirus (SARS-CoV-2) molecules. The role of the viral spike glycoprotein (S-protein) has been clearly established in SARS-CoV-2 infection through its capacity to bind to the host cell surface heparan sulfate proteoglycan (HSPG) and angiotensin-converting enzyme-2. The antiviral strategies targeting these 2 virus receptors are currently under intense investigation.

Safety and Pharmacokinetics of Intranasally Administered Heparin.

Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.

Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring.

Safety and Pharmacokinetics of Intranasally Administered Heparin.

Purpose: Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.

Methods: Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring.

Structural and kinetic analyses of holothurian sulfated glycans suggest potential treatment for SARS-CoV-2 infection.

Certain sulfated glycans, including those from marine sources, can show potential effects against SARS-CoV-2. Here, a new fucosylated chondroitin sulfate (FucCS) from the sea cucumber Pentacta pygmaea (PpFucCS) (MW ∼10-60 kDa) was isolated and structurally characterized by NMR. PpFucCS is composed of {→3)-β-GalNAcX-(1→4)-β-GlcA-[(3→1)Y]-(1→}, where X = 4S (80%), 6S (10%) or nonsulfated (10%), Y = α-Fuc2,4S (40%), α-Fuc2,4S-(1→4)-α-Fuc (30%), or α-Fuc4S (30%), and S = SO.

Antiviral activities of four marine sulfated glycans against adenovirus and human cytomegalovirus.

Broad-spectrum antivirals are more needed than ever to provide treatment options for novel emerging viruses and for viruses that lack therapeutic options or have developed resistance. A large number of viruses rely on charge-dependent non-specific interactions with heparan sulfate (HS), a highly sulfated glycosaminoglycan (GAG), for attachment to cell surfaces to initiate cell entry. As such, inhibitors targeting virion-HS interactions have potential to have broad-spectrum antiviral activity.

Marine Antithrombotics.

Thrombosis remains a prime reason of mortality worldwide. With the available antithrombotic drugs, bleeding remains the major downside of current treatments. This raises a clinical concern for all patients undergoing antithrombotic therapy.

Design of therapeutically improved analogue of the antimicrobial peptide, indolicidin, using a glycosylation strategy.

Indolicidin is a member of cathelicidin family which displays broad spectrum antimicrobial activity. Severe toxicity and aggregation propensity associated with indolicidin pose a huge limitation to its probable therapeutic application. We are reporting the use of glycosylation strategy to design an analogue of indolicidin and subsequently explore structural and functional effects of sugar on it.

Effect of distal sugar and interglycosidic linkage of disaccharides on the activity of proline rich antimicrobial glycopeptides.

The effect of glycosylation on protein structure and function depends on a variety of intrinsic factors including glycan chain length. We have analyzed the effect of distal sugar and interglycosidic linkage of disaccharides on the properties of proline-rich antimicrobial glycopeptides, formaecin I and drosocin. Their glycosylated analogs-bearing lactose, maltose and cellobiose, as a glycan side chain on their conserved threonine residue, were synthesized where these disaccharides possess identical proximal sugar and vary in the nature of distal sugar and/or interglycosidic linkage.