A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

Sisi Kang; Mei Yang; Suhua He; Yueming Wang; Xiaoxue Chen; Yao-Qing Chen; Zhongsi Hong; Jing Liu; Guanmin Jiang; Qiuyue Chen; Ziliang Zhou; Zhechong Zhou; Zhaoxia Huang; Xi Huang; Huanhuan He; Weihong Zheng; Hua‐Xin Liao; Fei Xiao; Hong Shan; Shoudeng Chen

doi:10.1038/s41467-021-23036-9

Molecular BiologyNature CommunicationsMay 11, 2021

Peer-reviewed journal article

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

Sisi Kang iD, Mei Yang iD, Suhua He iD, Yueming Wang iD, Xiaoxue Chen iD, Yao-Qing Chen iD, Zhongsi Hong iD, Jing Liu iD, Guanmin Jiang iD, Qiuyue Chen, Ziliang Zhou iD, Zhechong Zhou, Zhaoxia Huang, Xi Huang iD, Huanhuan He iD, Weihong Zheng iD, Hua‐Xin Liao iD, Fei Xiao iD, Hong Shan iD, Shoudeng Chen iD

Abstract

Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.

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