Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
Institute of Biomedicine, Jinan University, Guangzhou, China.
Nat Commun. 2021 May 11;12(1):2697. doi: 10.1038/s41467-021-23036-9.
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.
虽然人类针对严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）核衣壳（N）蛋白产生的抗体在感染后会被显著增强，但人们对 N 反应性抗体的功能知之甚少。在此，我们从一位快速康复的 COVID-19 患者中分离并鉴定了一组 32 种 N 蛋白特异性单克隆抗体（mAb），该患者对 SARS-CoV-2 N 蛋白的抗体反应强于对 SARS-CoV-2 刺突（S）蛋白的抗体反应。与具有最高结合亲和力的 mAb（nCoV396）的 N 蛋白 RNA 结合域的复合物结构揭示了表位和抗原变构调节的变化。功能上，无病毒补体超激活分析表明，nCoV396 特异性地破坏了 N 蛋白诱导的补体超激活，这是 COVID-19 患者发病率和死亡率的一个风险因素，从而为鉴定功能性抗 N 蛋白 mAb 奠定了基础。
