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

Prophylactic and Therapeutic Serum Concentrations of Unfractionated Heparin (UFH)

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.

Learn Before

Related

Learn After