Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Lung Heparin and Porcine Intestine Heparin

Guan, Yudong; Xu, Xiaohui; Liu, Xinyue; Sheng, Anran; Jin, Lan; Linhardt, Robert J.

doi:10.1016/j.xphs.2016.03.037

Cited by 31 publications

(29 citation statements)

References 25 publications

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“…Based on our discovery of GAG-binding and GAGbinding-like motifs at site 1 (within the RBD, Y453-S459), site 2 (at the proteolytic cleavage site at S1/S2 junction, P681-S686), and site 3 (at the S2' proteolytic cleavage site, S810-S816), we hypothesized that SARS-CoV-2 may also interact with host cell surface GAGs through its SGPs to invade host cell (Fig 1, S2 Fig, S3 Fig). The predominant GAG in normal human lung is HS followed by CS [22] and it is noteworthy that lung tissue is rich in mast cells and has been a source of commercial HP [23]. Using unbiased docking, we found that TriS HS hexasaccharide 5D).…”

Section: Discussionmentioning

confidence: 94%

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Kim

Jin

Sood

et al. 2020

Preprint

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Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAGbinding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development.was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission.

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Section: Discussionmentioning

confidence: 94%

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Kim

Jin

Sood

et al. 2020

Preprint

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“…Similar differences, between porcine intestinal, bovine lung, and bovine intestinal heparins, had been previously reported by our laboratory. 17,18 Three independent batches of LMWHs were prepared from a single lot of both bovine lung and bovine intestinal heparin using a chemical b-eliminative process modeled on that thought to be used for the preparation of Lovenox ( Figure 1). The molecular weight and activity properties of these 6 batches of LMWH were examined ( Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…4,9 Over the past 25 years, there have been major technological advances in the chemical analysis of complex mixtures of polysaccharides, owing primarily to advances in nuclear magnetic resonance (NMR) [10][11][12] and mass spectrometry (MS). [13][14][15][16][17] These advances have led to bottom-up 14 and top-down analysis 15 of these complex mixtures of polysaccharides that allow the detailed comparison of heparins and LMWHs produced from different tissues, species, sources, and by different processes. [17][18][19] In the current study, we examine an LMWH prepared from bovine intestinal and bovine lung heparins using a process commonly applied to produce the LMWH, enoxaparin (Lovenox), from porcine intestinal heparin.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Heparins With Enoxaparin

Ange

Fareed

Hoppensteadt

et al. 2017

Clin Appl Thromb Hemost

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Heparin and its low-molecular-weight heparin (LMWH) derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine. The worldwide dependence on a single animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including bovine tissues such as bovine intestine or lung. A number of laboratories are currently examining the similarities and differences between heparins prepared from porcine and bovine tissues. The current study is designed to compare LMWH prepared from bovine heparins through chemical β-elimination, a process currently used to prepare the LMWH, enoxaparin, from porcine heparin. Using top-down, bottom-up, compositional analysis and bioassays, LMWHs, derived from bovine lung and intestine, are shown to closely resemble enoxaparin.

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“…Note that because of the foreseeable shortage of intestinal porcine mucosa as source for heparin (the raw product for the production of LMWHs), expansion to other animal tissues seems necessary. Currently, porcine intestine is the only approved source for producing LMWHs in most countries . Enoxaparin prepared from ovine heparin closely resembles branded enoxaparin and will soon be tested clinically …”

Section: Methodsmentioning

confidence: 99%

“…Currently, porcine intestine is the only approved source for producing LMWHs in most countries. 21 Enoxaparin prepared from ovine heparin closely resembles branded enoxaparin and will soon be tested clinically. 22 The development of new synthetic oligosaccharides, in addition to pentasaccharides, were published, which can possibly replace biological LMWHs in the future.…”

Section: Quality Aspects: Molecular Structure Of Lmwhs and New Sophmentioning

confidence: 99%

Biosimilars of low molecular weight heparins: Relevant background information for your drug formulary

Brouwers

Lennep

Beinema

2019

Brit J Clinical Pharma

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Biosimilars of low molecular weight heparins (LMWHs) are more alike the originator than different branded LMWHs. The latter differ largely in molecular weight, anti‐FXa/anti‐FIIa ratio and antithrombin binding. The Food and Drug Administration and European Medicines Agency guidelines are sufficient for the clinical use of high quality LMWHs. However, the Food and Drug Administration guideline lacks the results of a phase I clinical trial in the approval process. Most information about biosimilars is available for enoxaparin given that many biosimilars of enoxaparin have received market access. The guidelines of many International Thrombosis Societies for LMWH biosimilars are too stringent, not updated and impractical for formulary uptake discussions. This review gives background information on critical factors for the formulary uptake process of LMWHs with special attention for the use of the System of Objectified Judgment Analysis/Infomatrix model.

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Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Lung Heparin and Porcine Intestine Heparin

Cited by 31 publications

References 25 publications

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry

Comparison of Low-Molecular-Weight Heparins Prepared From Bovine Heparins With Enoxaparin

Biosimilars of low molecular weight heparins: Relevant background information for your drug formulary

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