Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
Ting Gao, Mingdong Hu, Xiaopeng Zhang, Hongzhen Li, Lin Zhu, Hainan Liu, Qincai Dong, Zhang Zhang, Zhongyi Wang, Yong Hu, Yangbo Fu, Yanwen Jin, Kaitong Li, Songtao Zhao, Yongjiu Xiao, Shuping Luo, Lufeng Li, Lingfang Zhao, Junli Liu, Huailong Zhao, Yue Liu, Weihong Yang, Jing Peng, Xiaoyu Chen, Ping Li, Yaoning Liu, Yonghong Xie, Jibo Song, Lu Zhang, Qingjun Ma, Xiuwu Bian, Wei Chen, Xuan Liu, Qing Mao, Cheng Cao
doi: https://doi.org/10.1101/2020.03.29.20041962
Abstract
An excessive immune response contributes to SARS-CoV, MERS-CoV and SARS-CoV-2 pathogenesis and lethality, but the mechanism remains unclear. In this study, the N proteins of SARS-CoV, MERS-CoV and SARS-CoV-2 were found to bind to MASP-2, the key serine protease in the lectin pathway of complement activation, resulting in aberrant complement activation and aggravated inflammatory lung injury. Either blocking the N protein:MASP-2 interaction or suppressing complement activation can significantly alleviate N protein-induced complement hyper-activation and lung injury in vitro and in vivo. Complement hyper-activation was also observed in COVID-19 patients, and a promising suppressive effect was observed when the deteriorating patients were treated with anti-C5a monoclonal antibody. Complement suppression may represent a common therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.
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