A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation.

Nature communications 2021 May 11

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Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

Citation

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. A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation. Nature communications. 2021 May 11;12(1):2697