CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 variants

 Zhi-Nan Chen, Ping Zhu, Huijie Bian, Jiejie Geng, Liang Chen, Yufeng Yuan, Ruo Chen, Ke Wang, Yongqiang Deng, Peng Du, Jiangning Liu, Guizhen Wu, Youchun Wang, Xiuxuan Sun, Ting Guo, Xu Yang, Jiao Wu, Jianli Jiang, Ling Li, Kui Zhang, Hua Zhu, Zhaohui Zheng, Xianghui Fu, Fengfan Yang, Xiaochun Chen, Hao Tang, Zheng Zhang, Ding Wei, Yang Zhang, Ying Shi, Yumeng Zhu, Zhuo Pei, Fei Huo, Shirui Chen, Qingyi Wang, Wen Xie, Yirong Li

doi: https://doi.org/10.1101/2021.05.14.444111

This article is a preprint and has not been certified by peer review [what does this mean?].

PDF: https://www.biorxiv.org/content/10.1101/2021.05.14.444111v1.full.pdf

Abstract

SARS-CoV-2 and its variants are raging worldwide. Unfortunately, the global vaccination is not efficient enough to attain a vaccine-based herd-immunity and yet no special and effective drug is developed to contain the spread of the disease. Previously we have identified CD147 as a novel receptor for SARS-CoV-2 infection. Here, we demonstrated that CD147 antibody effectively inhibits infection and cytokine storm caused by SARS-CoV-2 variants. In CD147KO VeroE6 cells, infections of SARS-CoV-2, its variants (B.1.1.7, B.1.351) and pseudovirus mutants (B.1.1.7, B.1.351, B.1.525, B.1.526 (S477N), B.1.526 (E484K), P.1, P.2, B.1.617.1, B.1.617.2) were decreased. Meanwhile, CD147 antibody effectively blocked the entry of variants and pseudomutants in VeroE6 cells, and inhibited the expression of cytokines. A model of SARS-CoV-2-infected hCD147 transgenic mice was constructed, which recapitulated the features of exudative diffuse alveolar damage and dynamic immune responses of COVID-19. CD147 antibody could effectively clear the virus and alveolar exudation, resolving the pneumonia. We found the elevated level of cyclophilin A (CyPA) in plasma of severe/critical cases, and identified CyPA as the most important proinflammatory intermediate causing cytokine storm. Mechanistically, spike protein of SARS-CoV-2 bound to CD147 and initiated the JAK-STAT pathway, which induced expression of CyPA. CyPA reciprocally bound to CD147, triggered MAPK pathway and consequently mediated the expression of cytokine and chemokine. In conclusion, CD147 is a critical target for SARS-CoV-2 variants and CD147 antibody is a promising drug to control the new wave of COVID-19 epidemic.

Competing Interest Statement

The authors have declared no competing interest.

https://www.biorxiv.org/content/10.1101/2021.05.14.444111v1