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

Abstract

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.

• Authors: 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
• Journal: Nature communications (Nat Commun) Vol. 12 Issue 1 Pg. 2697 (05 11 2021) ISSN: 2041-1723 [Electronic] England
• PMID: 33976229 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Viral
• Antigen-Antibody Complex
• Coronavirus Nucleocapsid Proteins
• Epitopes
• Phosphoproteins
• nucleocapsid phosphoprotein, SARS-CoV-2

Topics

• Allosteric Regulation
• Antibodies, Monoclonal (chemistry, immunology)
• Antibodies, Viral (chemistry, immunology, pharmacology)
• Antibody Affinity
• Antigen-Antibody Complex (chemistry)
• COVID-19 (immunology)
• Complement Activation (drug effects)
• Convalescence
• Coronavirus Nucleocapsid Proteins (chemistry, immunology)
• Crystallography, X-Ray
• Epitopes
• Humans
• Phosphoproteins (chemistry, immunology)
• Protein Conformation
• SARS-CoV-2 (immunology)