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. While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.
【저자키워드】 antibodies, SARS-CoV-2, X-ray crystallography, Complement cascade, 【초록키워드】 COVID-19, coronavirus disease, coronavirus, S protein, antibody, Antibody Response, monoclonal antibody, Infection, complement, risk factor, severe acute respiratory syndrome Coronavirus, monoclonal antibodies, binding affinity, RNA, Protein, Epitopes, Coronavirus disease-19, nucleocapsid, morbidity, N protein, SARS-CoV-2 N protein, morbidity and mortality, respiratory, crystal structure, epitope, COVID-19 patients, mAbs, convalescent patient, SARS-CoV-2 spike, mAb, SARS-CoV-2 S protein, Analysis, allosteric regulation, acute respiratory syndrome, Regulation, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, complex, highest binding affinity, foundation, binding domain, Hyperactivation, while, dominant, functional, changes in, reveal, elicited, the N protein, the SARS-CoV-2, 【제목키워드】 complement, SARS-CoV-2 antibody, nucleocapsid, Hyperactivation,