A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

Kang, S.; Yang, M.; He, S.; Wang, Y.; Chen, X.; Chen, Y.; Hong, Z.; Liu, J.; Jiang, G.; Chen, Q.; Zhou, Z.; Huang, Z.; Huang, X.; He, H.; Zheng, W.; Liao, H.-X.; Xiao, F.; Shan, H.; Chen, S.

doi:10.1101/2020.09.10.292318

bioRxiv · 10.1101/2020.09.10.292318

A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation

Kang, S.·Yang, M.·He, S.·Wang, Y.·Chen, X.·Chen, Y.·Hong, Z.·Liu, J.·Jiang, G.·Chen, Q.·Zhou, Z.·Huang, Z.·Huang, X.·He, H.·Zheng, W.·Liao, H.-X.·Xiao, F.·Shan, H.·Chen, S.

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Abstract

Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigens allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence SummaryB cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein.

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Kang, S., Yang, M., He, S., Wang, Y., Chen, X., Chen, Y., Hong, Z., Liu, J., Jiang, G., Chen, Q., Zhou, Z., Huang, Z., Huang, X., He, H., Zheng, W., Liao, H.-X., Xiao, F., Shan, H., Chen, S.. 2020-09-11. A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation. https://doi.org/10.1101/2020.09.10.292318

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