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.
View Article and Find Full Text PDFTamarind seed polysaccharide (TSP) is a neutral water-soluble galactoxyloglucan isolated from the seed kernel of 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.
View Article and Find Full Text PDFHyaluronic acid (HA) is a natural and biocompatible polysaccharide that is able to interact with CD44 receptors to regulate inflammation, fibrosis, and tissue reconstruction. It is a suitable chemical scaffold for drug delivery that can be functionalized with pharmacophores and/or vectorizable groups. The derivatization of HA is achieved to varying extents by reacting 1-amino-1-deoxy-lactitol via the carboxyl group to form amide linkages, giving rise to the grafted polymer, HYLACH.
View Article and Find Full Text PDFThe 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.
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