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Unfractionated heparin inhibits live wild-type SARS-CoV-2 cell infectivity at therapeutically relevant concentrations.
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  • Julia Tree,
  • Jeremy Turnbull,
  • Karen Buttigieg,
  • Michael Elmore,
  • Naomi Coombes,
  • John Hogwood,
  • Edwin Yates,
  • Elaine Gray,
  • Dave Singh,
  • Tom Wilksinson,
  • Clive Page,
  • Miles Carroll
Julia Tree
Public Health England Porton
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Jeremy Turnbull
University of Liverpool
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Karen Buttigieg
Public Health England Porton
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Michael Elmore
Public Health England Porton
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Naomi Coombes
Public Health England Porton
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John Hogwood
National Institute for Biological Standards and Control
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Edwin Yates
University of Liverpool
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Elaine Gray
National Institute for Biological Standards and Control
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Dave Singh
University of Manchester
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Tom Wilksinson
University of Southampton Faculty of Medicine
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Clive Page
king's college london
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Miles Carroll
Public Health England Porton
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Abstract

Background and Purpose: Currently there are no licensed vaccines and limited antivirals for the treatment of COVID-19. Heparin (delivered systemically) is currently being used to treat anticoagulant anomalies in COVID-19 patients. In addition, in the UK, nebulised unfractionated heparin (UFH) is currently being trialled in COVID-19 patients as a potential treatment. A systematic comparison of the potential antiviral effect of various heparin preparations on live wild-type SARS-CoV-2, in vitro, is thus urgently needed. Experimental Approach: A range of heparin preparations both UFH (n=4) and low molecular weight heparins (LMWH) (n=3) of porcine or bovine origin were screened for antiviral activity against live SARS-CoV-2 (Victoria/01/2020) using a plaque reduction neutralisation assay and Vero E6 cells. ND50 values for each heparin were calculated using a mid-point probit analysis. Key Results: UFH had potent antiviral effects, with ND50 values of 12.5 and 23 μg/ml for two porcine mucosal UFH tested. Bovine mucosal UFH had similar antiviral effects although it was ~50% less active (ND50, 50-75 μg/ml). In contrast, LMWHs such as Clexane and Fragmin were markedly less active by ~100-fold (ND50 values of 2.6-6.8 mg/ml). Conclusions and Implications: This comparison of a panel of clinically relevant heparins, including the UFH preparation under trial in the UK, demonstrated that distinct products exhibit different degrees of antiviral activity against live SARS-CoV-2. Porcine mucosal UFH has the strongest antiviral activity followed by bovine mucosal UFH, whereas LMWHs had the lowest amount of antiviral activity (by 100-fold). Overall the data strongly support further clinical investigation of UFH as a potential treatment for patients with COVID-19.

Peer review status:IN REVISION

13 Jul 2020Submitted to British Journal of Pharmacology
17 Jul 2020Assigned to Editor
17 Jul 2020Submission Checks Completed
18 Jul 2020Reviewer(s) Assigned
13 Aug 2020Review(s) Completed, Editorial Evaluation Pending
20 Aug 2020Editorial Decision: Revise Minor
22 Sep 20201st Revision Received