Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
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. One Sentence SummaryThe lectin pathway of complement activation is a promising target for the treatment of highly pathogenic coronavirus induced pneumonia.
Zhao Lingfang、Wang Zhongyi、Li Lufeng、Gao Ting、Hu Mingdong、Zhang Xiaopeng、Zhu Lin、Liu Hainan、Jin Yanwen、Xiao Yongjiu、Luo Shuping、Liu Junli、Peng Jing、Liu Yaoning、Liu Yue、Song Jibo、Yang Weihong、Xie Yonghong、Chen Wei、Zhao Huailong、Zhang Lu、Zhang Zhang、Li Kaitong、Fu Yangbo、Mao Qing、Cao Cheng、Ma Qingjun、Liu Xuan、Bian Xiuwu、Li Ping、Zhao Songtao、Hu Yong、Chen Xiaoyu、Dong Qincai、Li Hongzhen
COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||The 940th Hospital of the People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology||COVID-19 Investigation Team dispatched to Wuhan by Beijing Institute of BiotechnologyFirst Affiliated Hospital, Army Medical University||COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologySecond Affiliated Hospital, Army Medical University||COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology||COVID-19 Investigation Team dispatched to Wuhan by Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyCOVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||The 940th Hospital of the People?ˉs Liberation ArmyThe 940th Hospital of the People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyFirst Affiliated Hospital, Army Medical University||COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyCOVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||Department of Gastroenterology, the 960th Hospital of the People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyCOVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||Department of Respiratory Disease, the Second Affiliated Hospital of Air Force Military Medical UniversityState Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology||COVID-19 Investigation Team dispatched to Wuhan by Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyCOVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||The 940th Hospital of the People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology||COVID-19 Investigation Team dispatched to Wuhan by Beijing Institute of BiotechnologyBeijing Key Laboratory of Bio-products Safety Assessment, Joinn Laboratories (China) Co. LtdState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyFirst Affiliated Hospital, Army Medical University||COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of Biotechnology||COVID-19 Investigation Team dispatched to Wuhan by Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyFirst Affiliated Hospital, Army Medical UniversityState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyFirst Affiliated Hospital, Army Medical University||COVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation ArmyState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyCOVID-19 Medical Team dispatched to Wuhan Huoshenshan Hospital by People?ˉs Liberation Army||Department of Anesthesiology, General Hospital of Northern Theater CommandState Key Laboratory of Pathogen Biosecurity, Beijing Institute of BiotechnologyBeijing Key Laboratory of Bio-products Safety Assessment, Joinn Laboratories (China) Co. Ltd
基础医学生物科学理论、生物科学方法生物科学研究方法、生物科学研究技术
Zhao Lingfang,Wang Zhongyi,Li Lufeng,Gao Ting,Hu Mingdong,Zhang Xiaopeng,Zhu Lin,Liu Hainan,Jin Yanwen,Xiao Yongjiu,Luo Shuping,Liu Junli,Peng Jing,Liu Yaoning,Liu Yue,Song Jibo,Yang Weihong,Xie Yonghong,Chen Wei,Zhao Huailong,Zhang Lu,Zhang Zhang,Li Kaitong,Fu Yangbo,Mao Qing,Cao Cheng,Ma Qingjun,Liu Xuan,Bian Xiuwu,Li Ping,Zhao Songtao,Hu Yong,Chen Xiaoyu,Dong Qincai,Li Hongzhen.Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation[EB/OL].(2025-03-28)[2025-05-18].https://www.medrxiv.org/content/10.1101/2020.03.29.20041962.点此复制
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