Author: Gao, Ting; Hu, Mingdong; Zhang, Xiaopeng; Li, Hongzhen; Zhu, Lin; Liu, Hainan; Dong, Qincai; Zhang, Zhang; Wang, Zhongyi; Hu, Yong; Fu, Yangbo; Jin, Yanwen; Li, Kaitong; Zhao, Songtao; Xiao, Yongjiu; Luo, Shuping; Li, Lufeng; Zhao, Lingfang; Liu, Junli; Zhao, Huailong; Liu, Yue; Yang, Weihong; Peng, Jing; Chen, Xiaoyu; Li, Ping; Liu, Yaoning; Xie, Yonghong; Song, Jibo; Zhang, Lu; Ma, Qingjun; Bian, Xiuwu; Chen, Wei; Liu, Xuan; Mao, Qing; Cao, Cheng
Title: Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation Cord-id: dxs8ggyh Document date: 2020_3_30
ID: dxs8ggyh
Snippet: 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 a
Document: 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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