Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation (original) (raw)

, 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.

One Sentence Summary The lectin pathway of complement activation is a promising target for the treatment of highly pathogenic coronavirus induced pneumonia.

Competing Interest Statement

The authors have declared no competing interest.

Clinical Trial

2020L00003

Funding Statement

National Science and Technology Major Projects (2018ZX09711003-005-005 and 2018ZX09201017-007), National Basic Research Program of China (2012CB518902)

Author Declarations

All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.

Yes

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

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Data Availability

All data is always available for researches interested in this study.