RT4 cells that were pre-treated with anti-ACE2 antibodies were introduced to UFH.  100nM S1S2 was completely inhibited by UFH with an IC50 of
0.033U/ml, a measurement of the potency of an inhibitor (95% confidence interval 0.016-0.07).  This potency value is well below the serum concentrations of UFH used to treat patients prophylactically and therapeutically.  

Unfractionated Heparin (UFH) Inhibits SARS-CoV-2 S Protein Below Prophylactic and Therapeutic Serum Concentrations in RT4 Cells

- Prophylactic concentration: 0.1-0.4U/ml
- Therapeutic concentration: 0.3-0.7U/ml

IU: international units (arbitrary amount)

Michigan State University

Anticoagulants like heparin may improve outcomes in COVID-19 patients. Many patients exhibit unusual clotting patterns that may be alleviated by use of anticoagulants.  Heparin has been shown to directly bind to the S1 subunit of SARS-CoV-2 S protein which may interfere with its ability to infect cells.

Heparin as a treatment for COVID-19

Partridge, L. J., Urwin, L., Nicklin, M. J., James, D. C., Green, L. R., & Monk, P. N. (2020). ACE2-independent interaction of SARS-CoV-2 spike protein to human epithelial cells can be inhibited by unfractionated heparin. bioRxiv.
https://www.biorxiv.org/content/10.1101/2020.05.21.107870v2
doi: 10.1101/2020.05.21.107870

ACE2-independent interaction of SARS-CoV-2 spike protein to human epithelial cells can be inhibited by unfractionated heparin

Overall, heparin use did not improve outcomes. However, in severe COVID-19 cases with a sepsis-induced coagulopathy (SIC)  score of 4 or higher and patients with D-dimer levels above 6 times normal levels, heparin treatment reduced 28-day mortality rates.

- results for heparin vs. no anticoagulants by SIC score
- results for heparin vs. no anticoagulants by D-dimer level
- results for univariate analysis for other clotting factors
- patient characteristics
- SIC score
- methods
- discussion

Findings supporting heparin use in COVID-19 patients for patients at high risk of coagulopathy from retrospective study in Wuhan, China

LMWHs include drugs such as dalteparin and enoxparin.

- Prophylactic concentration:  0.2-0.5IU/ml
- Therapeutic concentration: 0.5-1.2IU/ml 

IU: international units (arbitrary amount)

Prophylactic and Therapeutic Serum Concentrations of Low Molecular Weight Heparins (LMWH)

Partridge et al. have observed multiple heparin binding sites on the SARS-CoV-2 S protein, including:

- one at the furin cleavage site between the S1 and S2 subunits
- others in the S2 domain 
- others in the receptor binding domain (RBD)

SARS-CoV-2 S Protein May Have Multiple Heparin Binding Sites

In RT4 cells pre-treated with anti-ACE2 antibodies, unfractionated heparin strongly inhibited SARS-CoV-2 S1S2 protein binding, whereas the low-molecular-weight heparins dalteparin and enoxaparin acted as partial inhibitors and were less potent than unfractionated heparin.

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