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Heparin - an old drug with multiple potential targets in Covid-19 therapy.

Published on May 19, 2020in Journal of Thrombosis and Haemostasis4.662
· DOI :10.1111/JTH.14898
Ulf Lindahl , Ulf Lindahl74
Estimated H-index: 74
(Uppsala University),
Jin-Ping Li38
Estimated H-index: 38
(Uppsala University)
Abstract
A prominent clinical feature of severe Covid-19 infection is respiratory failure associated with pulmonary coagulopathy. Recent reports published in Thrombosis and Haemostasis show that treatment with low-molecular weight heparin (LMWH) decreases mortality in critically ill patients with sepsis-induced hypercoagulation, and thus argue for prophylactic administration of the anticoagulant. In addition, the authors point to non-anticoagulant activities of heparin, in particular anti-inflammatory effects with potential to prevent deterioration of the disease. We would like to use this opportunity to clarify the biochemical background of the diverse activities of heparin, and further, how this information may be exploited to generate more efficient treatment of the viral infection. Mechanisms to consider relate to the functional roles of proteins interacting with heparan sulfate (HS), a polysaccharide closely related to heparin.
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A major global effort is currently ongoing to search for therapeutics and vaccines to treat or prevent infection by the SARS-CoV-2 virus. Repurposing existing entities is one attractive approach. The heparan sulfate mimetic pixatimod is a clinical-stage synthetic sulfated compound that is a potent inhibitor of the glycosidase heparanase, and has known anti-cancer, anti-inflammatory and also antiviral properties. Here we show that pixatimod binds directly to the SARS-CoV-2 spike protein S1 recept...
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#2Fanny Vardon-Bounes (University of Toulouse)H-Index: 1
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Abstract The novel Corona virus infection (Covid-19) first identified in China in December 2019 has rapidly progressed in pandemic leading to significant mortality and unprecedented challenge for healthcare systems. Although the clinical spectrum of Covid-19 is variable, acute respiratory failure and systemic coagulopathy are common in severe Covid-19 patients. Lung is an important target of the SARS-CoV-2 virus causing eventually acute respiratory distress syndrome associated to a thromboinflam...
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#1Yang Yang (UMass: University of Massachusetts Amherst)H-Index: 1
#2Yi Du (UMass: University of Massachusetts Amherst)
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The emergence and rapid proliferation of the novel coronavirus (SARS-CoV-2) resulted in a global pandemic, with over six million cases and nearly four hundred thousand deaths reported worldwide by the end of May 2020. A rush to find the cures prompted re-evaluation of a range of existing therapeutics vis-a-vis their potential role in treating COVID-19, placing a premium on analytical tools capable of supporting such efforts. Native mass spectrometry (MS) has long been a tool of choice in support...
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#2Mark F. McCartyH-Index: 26
The high rate of thrombotic complications associated with COVID-19 seems likely to reflect viral infection of vascular endothelial cells, which express the ACE2 protein that enables SARS-CoV-2 to invade cells. Various proinflammatory stimuli can promote thrombosis by inducing luminal endothelial expression of tissue factor (TF), which interacts with circulating coagulation factor VII to trigger extrinsic coagulation. The signalling mechanism whereby these stimuli evoke TF expression entails acti...
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#1Jecko Thachil (University of Manchester)H-Index: 5
#1Jecko Thachil (University of Manchester)H-Index: 20
I thank Lindahl and Li for their thoughtful comments on the non-anticoagulant properties of heparin.1 Heightened awareness of hypercoagulability has made heparin part and parcel of the COVID-19 management algorithms. In addition, reports of prophylactic anticoagulation failure have triggered several trials where escalated doses of heparin are compared with standard doses with the aim of preventing thrombotic complications. At this juncture, we do need to consider where do the non-anticoagulant p...
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