A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation.
A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation.
复制标题
SARS-CoV-2 抗体可抑制病毒核衣壳蛋白诱导的补体过度激活
DOI：
10.1038/s41467-021-23036-9
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发表时间：
2021-05-11
影响因子：
16.6
通讯作者：
Chen S
中科院分区：
文献类型：
--
作者：
Kang S;Yang M;He S;Wang Y;Chen X;Chen YQ;Hong Z;Liu J;Jiang G;Chen Q;Zhou Z;Zhou Z;Huang Z;Huang X;He H;Zheng W;Liao HX;Xiao F;Shan H;Chen S
尽管由严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）核衣壳（N）蛋白引起的人类抗体在感染后显著增强，但对N反应性抗体的功能知之甚少。在此，我们从快速恢复的冠状病毒疾病-19（COVID-19）康复期患者中分离并分析了一组32 N蛋白特异性单克隆抗体（mAb），该患者对SARS-CoV-2 N蛋白而不是SARS-CoV-2刺突（S）蛋白具有显性抗体应答。具有最高结合亲和力mAb（nCoV 396）的N蛋白RNA结合结构域的复杂结构揭示了表位和抗原变构调节的变化。在功能上，无病毒补体超活化分析表明，nCoV 396特异性地损害N蛋白诱导的补体超活化，这是COVID-19患者发病和死亡的风险因素，从而为鉴定功能性抗N蛋白mAb奠定了基础。虽然SARS-CoV-2 S蛋白靶向单克隆抗体（mAb）的研究很好，很少有人知道N蛋白靶向mAb。在这里，Kang等人用来自恢复期患者的mAb提供了N蛋白RNA结合结构域的晶体结构，并表明它损害了N蛋白诱导的补体超活化。
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. While SARS-CoV-2 S protein targeting monoclonal antibodies (mAbs) are well studied, little is known about N protein-targeting mAbs. Here, Kang et al. provide the crystal structure of the N protein RNA binding domain with a mAb derived from a convalescent patient and show that it compromises the N protein-induced complement hyperactivation.
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DOI：
10.15252/embj.2020106478
发表时间：
2020-12-15
期刊：
The EMBO journal
影响因子：
--
作者：
Perdikari TM;Murthy AC;Ryan VH;Watters S;Naik MT;Fawzi NL
通讯作者：
Fawzi NL
影响因子：
8
作者：
McAndrews, Kathleen M.;Dowlatshahi, Dara P.;Kalluri, Raghu
通讯作者：
Kalluri, Raghu
影响因子：
13.2
作者：
Sun, Baoqing;Feng, Ying;Chen, Ling
通讯作者：
Chen, Ling
影响因子：
3.6
作者：
Duncan, Renee C.;Bergstrom, Frida;Pike, Robert N.
通讯作者：
Pike, Robert N.
影响因子：
3.7
作者：
Morris L;Chen X;Alam M;Tomaras G;Zhang R;Marshall DJ;Chen B;Parks R;Foulger A;Jaeger F;Donathan M;Bilska M;Gray ES;Abdool Karim SS;Kepler TB;Whitesides J;Montefiori D;Moody MA;Liao HX;Haynes BF
通讯作者：
Haynes BF