CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis

Zihan Tang, Yanyan Xu, Yun Tan, Hui Shi, Peipei Jin, Yunqi Li, Jialin Teng, Honglei Liu, Haoyu Pan, Qiongyi Hu, Xiaobing Cheng, Junna Ye, Yutong Su, Yue Sun, Jianfen Meng, Zhuochao Zhou, Huihui Chi, Xuefeng Wang, Junling Liu, Yong Lu, Feng Liu (), Jing Dai (), Chengde Yang (), Saijuan Chen () and Tingting Liu ()
Additional contact information
Zihan Tang: Shanghai Jiao Tong University School of Medicine
Yanyan Xu: Shanghai Jiao Tong University School of Medicine
Yun Tan: Shanghai Jiao Tong University School of Medicine
Hui Shi: Shanghai Jiao Tong University School of Medicine
Peipei Jin: Shanghai Jiao Tong University School of Medicine
Yunqi Li: Shanghai Jiao Tong University School of Medicine
Jialin Teng: Shanghai Jiao Tong University School of Medicine
Honglei Liu: Shanghai Jiao Tong University School of Medicine
Haoyu Pan: Shanghai Jiao Tong University School of Medicine
Qiongyi Hu: Shanghai Jiao Tong University School of Medicine
Xiaobing Cheng: Shanghai Jiao Tong University School of Medicine
Junna Ye: Shanghai Jiao Tong University School of Medicine
Yutong Su: Shanghai Jiao Tong University School of Medicine
Yue Sun: Shanghai Jiao Tong University School of Medicine
Jianfen Meng: Shanghai Jiao Tong University School of Medicine
Zhuochao Zhou: Shanghai Jiao Tong University School of Medicine
Huihui Chi: Shanghai Jiao Tong University School of Medicine
Xuefeng Wang: Shanghai Jiao Tong University School of Medicine
Junling Liu: Shanghai Jiao Tong University School of Medicine
Yong Lu: Shanghai Jiao Tong University School of Medicine
Feng Liu: Shanghai Jiao Tong University School of Medicine
Jing Dai: Shanghai Jiao Tong University School of Medicine
Chengde Yang: Shanghai Jiao Tong University School of Medicine
Saijuan Chen: Shanghai Jiao Tong University School of Medicine
Tingting Liu: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

Date: 2023
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DOI: 10.1038/s41467-023-40824-7

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