SARS-CoV-2 spike protein causes blood coagulation, thrombosis by competitive binding to heparan sulfate

 YiZhenga1JinxiangZhaob1JiaqiLia1ZhimouGuoaJiajingShengbXianlongYeaGaowaJinaChaoranWangaWengangChaicJingyuYanaDongLiubXinmiaoLianga

DOI: https://doi.org/10.1016/j.ijbiomac.2021.10.112

PDF: https://www.sciencedirect.com/science/article/pii/S0141813021022704/pdfft?md5=8bc46c4cad3a72d2000107daa81fe36d&pid=1-s2.0-S0141813021022704-main.pdf

Highlights

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S protein competitively binds to HS/heparin inducing an increase in thrombin activity.

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S protein directly promoted blood coagulation and thrombosis in zebrafish model.

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Exogenous heparin and HS significantly reduced the coagulation caused by S protein.

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.

https://www.sciencedirect.com/science/article/pii/S0141813021022704#!