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The risk of heparin shortage opens up the possibility of diversifying the sources of heparin by introducing products of other animal/organ origins. In addition to bovine heparin, already used in the past in the United States and Europe, ovine heparin can become another alternative to the widely used pig source. It is therefore appropriate to compare the anticoagulant activity of pig heparin with that of products of different animal origin and to verify whether blended heparin obtained from different sources can give rise to anticoagulant effects comparable to those of heparin of a single origin.

Tamarind seed polysaccharide (TSP) is a neutral water-soluble galactoxyloglucan isolated from the seed kernel of Tamarindus indica with average molecular weight (Mw) 600–800 kDa. The high viscosity of TSP slows solubilisation, and the absence of charged substituent hinders the formation of electrostatic interactions with biomolecules. TSP was sulphated in a one-step process using dimethylformamide as a solvent, and sulphur trioxide-pyridine complex as a sulphating reagent. Studies of chemical structure, molecular weight distribution and viscosity were conducted to characterise the synthesised products. The sulphation degree was established by conductimetric titration; the sulphate group distribution was studied by NMR spectroscopy and liquid chromatography-mass spectrometry, and sulphated TSP oligomers were obtained by enzymatic degradation with cellulase and/or xyloglucanase. Sulphated products showed higher solubility than TSP, Mws in the range of 700–1000 kDa, a sulphation degree of two to four per subunit and pseudoplastic behaviour. A preliminary study of mucoadhesion revealed the unexpected interaction of S-TSP with mucin, providing a route by which sulphated TSP interactions with biomolecules may be influenced.

With increasing urban expansion and population growth, coastal urban areas will be increasingly affected by climate change impacts such as extreme storm events, sea level rise and coastal flooding. To address coastal inundation risk for impact studies, integrated approaches accounting for flood hazard modelling, exposure and vulnerability of human and environmental systems are crucial. In this study, we model the impacts of sea level rise on coastal inundation depth for County Dublin, the most extensively urbanized area in Ireland, for the current period and for 2100 under two Representative Concentration Pathways RCP 4.5 and 8.5. A risk-centred approach has been considered by linking the information on coastal flood-prone areas to the exposure of the urban environment, in terms of potential future land cover changes, and to the socioeconomic vulnerability of the population. The results suggest significant challenges for Dublin city and the surrounding coastal areas, with an increase of around 26% and 67% in the number of administrative units considered at very high risk by the end of the century under a RCP 4.5 and 8.5, respectively. This study aims to contribute to existing coastal inundation research undertaken for Ireland by (i) providing a first-level screening of flooding hazards in the study area, (ii) demonstrating how land cover changes and socioeconomic vulnerability can contribute to the level of experienced risk and (iii) informing local authorities and at-risk communities so as to support them in the development of plans for adaptation and resilience.

The heparan sulfate (HS)-rich extracellular matrix (ECM) serves as an initial interaction site for the homotrimeric spike (S) protein of SARS-CoV-2 to facilitate subsequent docking to angiotensin-converting enzyme 2 (ACE2) receptors and cellular infection. More recent variants, notably Omicron, have evolved by swapping several amino acids to positively charged residues to enhance the interaction of the S-protein trimer with the negatively charged HS. However, these enhanced interactions may reduce Omicron’s ability to move through the HS-rich ECM to effectively find ACE2 receptors and infect cells, raising the question of how to mechanistically explain HS-associated viral movement. In this work, we show that Omicron S proteins have evolved to balance HS interaction stability and dynamics, resulting in enhanced mobility on an HS-functionalized artificial matrix. This property is achieved by the ability of Omicron S-proteins to cross-link at least two HS chains, allowing direct S-protein switching between chains as a prerequisite for cell surface mobility. Optimized HS interactions can be targeted pharmaceutically, as an HS mimetic significantly suppressed surface binding and cellular infection specifically of the Omicron variant. These findings suggest a robust way to interfere with SARS-CoV-2 Omicron infection and potentially future variants.

Heparan sulfate proteoglycans serve as initial attachment sites for several viruses and bacteria. Recent studies suggest that SARS-CoV-2 similarly exploits these glycosaminoglycans, facilitating conformational changes in the spike protein that promote the interaction between the receptor-binding domain (S1-RBD) and the cellular angiotensin-converting enzyme 2 receptor (ACE2), thereby triggering the virus internalization process. The molecular details that drive this process, particularly the co-receptor role of heparan sulfate (HS), remain incompletely understood. The interaction between an HS hexasaccharide (hexa) and the N343 glycosylated S1-RBD of the wild-type (WT) and Omicron variant of SARS-CoV-2 was investigated. The conformational properties of hexa with these S1-RBDs in unbound and bound states are explored using multiple independent MD simulations; the protein binding epitope of hexa, as well as the details of its interaction with S1-RBD of the Omicron variant, are characterized by comparing experimental and theoretical 1H STD NMR signals. This investigation identifies the role played by the glycosyl moiety at N343 in potentially affecting this interaction in both WT and Omicron S1-RBD, explaining the observed low specificity and multi-modal nature of the interaction between HS oligosaccharides and these S1-RBDs.

The scope of this article is to provide a brief general introduction to heparan sulfate (HS) and heparin, and attempt to identify some of the central challenges regarding research into the chemistry and biology of glycosaminoglycans (GAGs), some of which are the subject of contributions to the special issue of Molecules (published in volume 23, 2018) entitled ‘Heparan Sulfate and Heparin: Challenges and Controversies’ [...]

The high transmissibility and mutation ability of coronaviruses enable them to easily escape existing immune protection and also pose a challenge to existing antiviral drugs. Moreover, drugs only targeting viruses cannot always attenuate the “cytokine storm”. Herein, a synthetic heparan sulfate (HS) mimetic, HMSA‐06 is reported, that exhibited antiviral activities against both the SARS‐CoV‐2 prototype and Omicron strains by targeting viral entry and replication. Of particular note, HMSA‐06 demonstrated more potent anti‐SARS‐CoV‐2 effects than PG545 and Roneparstat. SARS‐CoV‐2 is reported to hijack autophagy to facilitate its replication, therefore boosting autophagy can attenuate SARS‐CoV‐2 infection. It is revealed that HMSA‐06, but not a similar HS mimetic that failed to inhibit SARS‐CoV‐2, can upregulate cellular autophagy flux. In addition, HMSA‐06 was found to robustly block the NLRP3‐mediated inflammatory reaction in SARS‐CoV‐2 infected THP‐1 derived macrophages as evidenced by a reduction in inflammasome formation and the subsequent decreased secretion of mature caspase‐1 and IL‐1β. The HMSA‐06's inflammation inhibitory function is further confirmed using a LPS/ATP‐stimulated THP‐1 macrophage model. Altogether, this study has identified a promising HS mimetic to combat SARS‐CoV‐2‐associated diseases by inhibiting viral infection and attenuating viral‐induced inflammatory reaction, providing insights into the development of novel anti‐coronavirus drugs in the future. This study identifies a unique HS mimetic, HMSA‐06, that inhibits different types of SARS‐CoV‐2 cell entry and viral replication by boosting autophagic flux, potentially serving as the first line of defense against COVID‐19. Additionally, HMSA‐06 significantly attenuates NLRP3 inflammasome activation, which may help mitigate hyperinflammation during the late stage of SARS‐CoV‐2 infection.

Ireland and the UK possess vast ocean energy resources within their respective maritime areas. However, not all offshore areas are suitable for deployment of ocean energy devices. This article describes the development of a multitude of geospatial data relating to ocean energy site suitability, as well as a Web-GIS tool for hosting and performing analysis on this data. A validation of wave, water depth and seabed character data used in the study revealed good correlation between modelled and in situ data. The data is mapped, and the spatial patterns are discussed with relevance to ORE sector implications. A site selection model, which included much of this data, was developed for this study and the Web-GIS tool. A survey conducted with ocean energy technology developers revealed their desired site criteria. The responses were applied in a case study using the site selection model to uncover potential and optimum areas for deployment of both wave and tidal energy devices. The results reveal extensive areas of the Atlantic Ocean and Celtic Sea appropriate for wave energy deployment and less extensive areas for tidal energy deployment, in the Irish Sea and Inner Seas off the West Coast of Scotland.

A number of low molecular weight heparin (LMWH) products are available for clinical use and although all share a similar mechanism of action, they are classified as distinct drugs because of the different depolymerisation processes of the native heparin resulting in substantial pharmacokinetic and pharmacodynamics differences. While enoxaparin has been extensively investigated, little information is available regarding the LMWH dalteparin. The present study is focused on the detailed structural characterization of Fragmin® by LC-MS and NMR applied both to the whole drug and to its enzymatic products. For a more in-depth approach, size homogeneous octasaccharide and decasaccharide components together with their fractions endowed with high or no affinity toward antithrombin were also isolated and their structural profiles characterized. The combination of different analytical strategies here described represents a useful tool for the assessment of batch-to-batch structural variability and for comparative evaluation of structural features of biosimilar products.

Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources.