A COVID-19 antibody curbs SARS-CoV-2 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 isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had 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 mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, 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..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 29. Juli Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kang, Sisi [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-106760/v1 |
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XRA033592810 |
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| 520 | |a 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 isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who had 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 mAb with the highest binding affinity (nCoV396) revealed changes in the epitopes and antigen’s allosteric regulation. Functionally, a virus-free complement hyper-activation analysis demonstrated that nCoV396 specifically compromises the N protein-induced complement hyper-activation, 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. | ||
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| 700 | 1 | |a Hong, Zhongsi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Guanmin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Qiuyue |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Ziliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Zhechong |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Zhaoxia |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Xi |e verfasserin |4 aut | |
| 700 | 1 | |a He, Huanhuan |e verfasserin |4 aut | |
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| 700 | 1 | |a Chen, Shoudeng |e verfasserin |4 aut | |
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