PUBLICATION
SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate
- Authors
- Zheng, Y., Zhao, J., Li, J., Guo, Z., Sheng, J., Ye, X., Jin, G., Wang, C., Chai, W., Yan, J., Liu, D., Liang, X.
- ID
- ZDB-PUB-211109-6
- Date
- 2021
- Source
- International journal of biological macromolecules 193(Pt B): 1124-1129 (Journal)
- Registered Authors
- Keywords
- Anticoagulant therapy, Coagulation, Heparan sulfate, SARS-CoV-2, Spike protein
- MeSH Terms
-
- Animals
- Blood Coagulation*
- Heparitin Sulfate*/chemistry
- Heparitin Sulfate*/metabolism
- Humans
- Mice
- Protein Binding
- SARS-CoV-2*/chemistry
- SARS-CoV-2*/metabolism
- Spike Glycoprotein, Coronavirus*/chemistry
- Spike Glycoprotein, Coronavirus*/metabolism
- Thrombosis/metabolism*
- PubMed
- 34743814 Full text @ Int. J. Biol. Macromol.
Citation
Zheng, Y., Zhao, J., Li, J., Guo, Z., Sheng, J., Ye, X., Jin, G., Wang, C., Chai, W., Yan, J., Liu, D., Liang, X. (2021) SARS-CoV-2 spike protein causes blood coagulation and thrombosis by competitive binding to heparan sulfate. International journal of biological macromolecules. 193(Pt B):1124-1129.
Abstract
Thrombotic complication has been an important symptom in critically ill patients with COVID-19. It has not been clear whether the virus spike (S) protein can directly induce blood coagulation in addition to inflammation. Heparan sulfate (HS)/heparin, a key factor in coagulation process, was found to bind SARS-CoV-2 S protein with high affinity. Herein, we found that the S protein can competitively inhibit the bindings of antithrombin and heparin cofactor II to heparin/HS, causing abnormal increase in thrombin activity. SARS-CoV-2 S protein at a similar concentration (~10 μg/mL) as the viral load in critically ill patients can cause directly blood coagulation and thrombosis in zebrafish model. Furthermore, exogenous heparin/HS can significantly reduce coagulation caused by S protein, pointing to a potential new direction to elucidate the etiology of the virus and provide fundamental support for anticoagulant therapy especially for the COVID-19 critically ill patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping