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Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19

Carina Conzelmann, Janis A Müller, Lukas Perkhofer, Konstantin MJ Sparrer, Alexander N Zelikin, Jan Münch and Alexander Kleger
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DOI: https://doi.org/10.7861/clinmed.2020-0351
Clin Med November 2020
Carina Conzelmann
AInstitute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
*equal contributions
Roles: PhD student
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Janis A Müller
BInstitute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
*equal contributions
Roles: postdoctoral fellow
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Lukas Perkhofer
CDepartment of Internal Medicine, Ulm University Hospital, Ulm, Germany
Roles: attending physician in gastroenterology
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Konstantin MJ Sparrer
DInstitute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
Roles: junior principal investigator
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Alexander N Zelikin
EDepartment of Chemistry and iNano Interdisciplinary Nanoscience Centre, Aarhus University, Aarhus, Denmark
#equal contribution and joint supervision
Roles: associate professor
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Jan Münch
FInstitute of Molecular Virology, Ulm University Medical Centre, Ulm, Germany
Roles: professor of molecular virology
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Alexander Kleger
GDepartment of Internal Medicine, Ulm University Hospital, Ulm, Germany
#equal contribution and joint supervision
Roles: professor of molecular oncology
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  • For correspondence: alexander.kleger@uni-ulm.de
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    Fig 1.

    Heparin inhibits SARS-CoV-2 plaque formation. a) 800,000 Vero E6 cells were seeded in a 12-well plate the day before infection to result in a 100% confluent cell monolayer. The next day, medium was removed, cells were washed once with PBS and medium containing heparin (Sigma-Aldrich) was added. Cells were then inoculated with SARS-CoV-2 isolate BetaCoV/Netherlands/01/NL/2020 (#010V-03903; European virus archive – global) in 500 μl and incubated for 2 h at 37°C with shaking every 15 to 30 min. Next, cells were overlaid with 1.5 ml of 0.8% Avicel RC-581 (FMC Corporation) in medium containing heparin and incubated for 3 days. Cells were fixed, stained with crystal violet and imaged. b) Virus-induced plaques shown in Fig 1a were counted. c) Cytopathic effect (CPE) was quantified using a custom ImageJ macro as the percentage of non-stained area within one well. Raw images were converted to greyscale, regions of interest (= one well) defined, automatic thresholding (Minimum algorithm) applied and total/white pixel areas calculated. Values represent means of two technical replicates ± sd.

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Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19
Carina Conzelmann, Janis A Müller, Lukas Perkhofer, Konstantin MJ Sparrer, Alexander N Zelikin, Jan Münch, Alexander Kleger
Clinical Medicine Nov 2020, 20 (6) e218-e221; DOI: 10.7861/clinmed.2020-0351

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Inhaled and systemic heparin as a repurposed direct antiviral drug for prevention and treatment of COVID-19
Carina Conzelmann, Janis A Müller, Lukas Perkhofer, Konstantin MJ Sparrer, Alexander N Zelikin, Jan Münch, Alexander Kleger
Clinical Medicine Nov 2020, 20 (6) e218-e221; DOI: 10.7861/clinmed.2020-0351
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  • Article
    • ABSTRACT
    • Introduction
    • Thromboembolic events during COVID-19
    • Potential advantage of inhaled heparin
    • Heparin exerts direct antiviral activity
    • Anti-inflammatory and anticoagulant effects of heparin in the lung
    • Conclusion
    • Acknowledgments
    • References
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