CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma
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Published:2021-09-25
Issue:1
Volume:6
Page:
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ISSN:2059-3635
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Container-title:Signal Transduction and Targeted Therapy
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language:en
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Short-container-title:Sig Transduct Target Ther
Author:
Geng Jiejie, Chen Liang, Yuan Yufeng, Wang Ke, Wang YouchunORCID, Qin ChuanORCID, Wu Guizhen, Chen Ruo, Zhang Zheng, Wei Ding, Du Peng, Zhang JunORCID, Lin Peng, Zhang Kui, Deng YongqiangORCID, Xu Ke, Liu Jiangning, Sun Xiuxuan, Guo Ting, Yang Xu, Wu Jiao, Jiang Jianli, Li Ling, Zhang Kun, Wang Zhe, Zhang Jing, Yan Qingguo, Zhu Hua, Zheng Zhaohui, Miao Jinlin, Fu Xianghui, Yang Fengfan, Chen Xiaochun, Tang Hao, Zhang Yang, Shi Ying, Zhu Yumeng, Pei Zhuo, Huo Fei, Liang Xue, Wang Yatao, Wang Qingyi, Xie Wen, Li Yirong, Shi Mingyan, Bian HuijieORCID, Zhu Ping, Chen Zhi-Nan
Abstract
AbstractSARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants—alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 μg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a “spike protein-CD147-CyPA signaling axis”: Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics
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