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 function of N-reactive antibodies. Herein, we isolate and profile a panel 32 N protein-specific monoclonal (mAbs) from quick recovery disease-19 (COVID-19) convalescent patient who has dominant antibody responses to SARS-CoV-2 rather than spike (S) protein. The complex structure RNA binding domain with highest affinity mAb (nCoV396) reveals changes in epitopes antigen’s allosteric regulation. Functionally, virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises protein-induced hyperactivation, which risk factor for morbidity mortality COVID-19 patients, thus laying foundation identification functional anti-N mAbs.