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


Posted: 2021-11-08 20:00:00
Int J Biol Macromol . 2021 Oct 29;S0141-8130(21)02270-4. doi: 10.1016/j.ijbiomac.2021.10.112. Online ahead of print. Yi Zheng 1 , Jinxiang Zhao 2 , Jiaqi Li 1 , Zhimou Guo 1 , Jiajing Sheng 2 , Xianlong Ye 1 , Gaowa Jin 1 , Chaoran Wang 1 , Wengang Chai 3 , Jingyu Yan 4 , Dong Liu 5 , Xinmiao Liang 6 Affiliations Expand Affiliations 1 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. 2 Nantong Laboratory of Development and Diseases, School of Life Science, Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Nantong University, Nantong 226019, China. 3 Glycosciences Laboratory, Faculty of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, United Kingdom. 4 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: yanjingyu@dicp.ac.cn. 5 Nantong Laboratory of Development and Diseases, School of Life Science, Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Nantong University, Nantong 226019, China. Electronic address: tom@ntu.edu.cn. 6 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: liangxm@dicp.ac.cn. Item in Clipboard Yi Zheng et al. Int J Biol Macromol. 2021. Show details Display options Display options Format Int J Biol Macromol . 2021 Oct 29;S0141-8130(21)02270-4. doi: 10.1016/j.ijbiomac.2021.10.112. Online ahead of print. Authors Yi Zheng 1 , Jinxiang Zhao 2 , Jiaqi Li 1 , Zhimou Guo 1 , Jiajing Sheng 2 , Xianlong Ye 1 , Gaowa Jin 1 , Chaoran Wang 1 , Wengang Chai 3 , Jingyu Yan 4 , Dong Liu 5 , Xinmiao Liang 6 Affiliations 1 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. 2 Nantong Laboratory of Development and Diseases, School of Life Science, Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Nantong University, Nantong 226019, China. 3 Glycosciences Laboratory, Faculty of Medicine, Imperial College London, Hammersmith Campus, London W12 0NN, United Kingdom. 4 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: yanjingyu@dicp.ac.cn. 5 Nantong Laboratory of Development and Diseases, School of Life Science, Co-innovation Center of Neuroregeneration, Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Nantong University, Nantong 226019, China. Electronic address: tom@ntu.edu.cn. 6 CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China. Electronic address: liangxm@dicp.ac.cn. Item in Clipboard CiteDisplay options Display options Format 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. Keywords: Anticoagulant therapy; Coagulation; Heparan sulfate; SARS-CoV-2; Spike protein. Copyright © 2021. Published by Elsevier B.V. [x] Cite Copy Format: Send To [x]

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