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.
Highlights
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
SARS-CoV-2 nasal swabs reverse transcription polymerase chain reaction (RT-primer chain reaction (PCR)) tests were used to confirm that all six COVID19 patients were negative for SARS-CoV-2 at the time of blood collection
Serum antibody titers to SARS-CoV-2 S and N proteins were measured by enzyme-linked immunosorbent assay (ELISA) (Fig. 1a, b) and the specific values of antibody titers can be found in Supplementary Table 1
Summary
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. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the etiology agent of COVID-19, is one of the most abundant viral structural proteins with multiple functions inside the viral particles, the host cellular environment, and ex vivo experiments[14,15,16,17,18,19,20]. Among these functions, a recent preprint study found that the SARS-CoV-2 N protein bound to mannan-binding lectin (MBL)-associated serine protease 2 (MASP-2) and resulted in complement hyperactivation and aggravated inflammatory lung injury[19]. Our work indicates that human N-targeting mAbs from COVID-19 convalescents play essential roles in inhibition of complement hyperactivation
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