Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation
Gao, T.; Hu, M.; Zhang, X.; Li, H.; Zhu, L.; Liu, H.; Dong, Q.; Zhang, Z.; Wang, Z.; Hu, Y.; Fu, Y.; Jin, Y.; Li, K.; Zhao, S.; Xiao, Y.; Luo, S.; Li, L.; Zhao, L.; Liu, J.; Zhao, H.; Liu, Y.; Yang, W.; Peng, J.; Chen, X.; Li, P.; Liu, Y.; Xie, Y.; Song, J.; Zhang, L.; Ma, Q.; Bian, X.; Chen, W.; Liu, X.; Mao, Q.; Cao, C.
Show 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.
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