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

• Published in: Nature communications Vol. 14; no. 1; pp. 5077 - 13
• Main Authors: Tang, Zihan, Xu, Yanyan, Tan, Yun, Shi, Hui, Jin, Peipei, Li, Yunqi, Teng, Jialin, Liu, Honglei, Pan, Haoyu, Hu, Qiongyi, Cheng, Xiaobing, Ye, Junna, Su, Yutong, Sun, Yue, Meng, Jianfen, Zhou, Zhuochao, Chi, Huihui, Wang, Xuefeng, Liu, Junling, Lu, Yong, Liu, Feng, Dai, Jing, Yang, Chengde, Chen, Saijuan, Liu, Tingting
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.08.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 13/1; 13/95; 14/1; 14/63; 49/90; 49/91; 631/80/304; 692/699/255/2514; 706/648/697; 82/1; 82/58; 96/31; CD36 antigen; Coagulation; COVID-19; Disorders; Env protein; Glycoproteins; Humanities and Social Sciences; Hyperactivity; Intravenous administration; MAP kinase; Mass spectrometry; Mass spectroscopy; multidisciplinary; NF-κB protein; Pharmacology; Platelets; Protein deficiency; Proteins; Science; Science (multidisciplinary); Serum levels; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Thromboembolism; Thrombosis
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-40824-7

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. Aberrant coagulation and thrombosis are associated with severe SARS-CoV-2 infection. Here, the authors show that the E protein are associated with coagulation disorders in COVID-19 patients and could directly enhance platelet activation and thrombosis through a CD36/p38 MAPK/NF-kB signaling axis.