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-Structure paper
タイトル | Structural basis for the synergistic neutralization of coxsackievirus B1 by a triple-antibody cocktail. |
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ジャーナル・号・ページ | Cell Host Microbe, Vol. 30, Issue 9, Page 1279-11294.e6, Year 2022 |
掲載日 | 2022年9月14日 |
著者 | Qingbing Zheng / Rui Zhu / Zhichao Yin / Longfa Xu / Hui Sun / Hai Yu / Yuanyuan Wu / Yichao Jiang / Qiongzi Huang / Yang Huang / Dongqing Zhang / Liqin Liu / Hongwei Yang / Maozhou He / Zhenhong Zhou / Yanan Jiang / Zhenqin Chen / Huan Zhao / Yuqiong Que / Zhibo Kong / Lizhi Zhou / Tingting Li / Jun Zhang / Wenxin Luo / Ying Gu / Tong Cheng / Shaowei Li / Ningshao Xia / |
PubMed 要旨 | Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. ...Coxsackievirus B1 (CVB1) is an emerging pathogen associated with severe neonatal diseases including aseptic meningitis, myocarditis, and pancreatitis and also with the development of type 1 diabetes. We characterize the binding and therapeutic efficacies of three CVB1-specific neutralizing antibodies (nAbs) identified for their ability to inhibit host receptor engagement. High-resolution cryo-EM structures showed that these antibodies recognize different epitopes but with an overlapping region in the capsid VP2 protein and specifically the highly variable EF loop. Moreover, they perturb capsid-receptor interactions by binding various viral particle forms. Antibody combinations achieve synergetic neutralization via a stepwise capsid transition and virion disruption, indicating dynamic changes in the virion in response to multiple nAbs targeting the receptor-binding site. Furthermore, this three-antibody cocktail protects against lethal challenge in neonatal mice and limits pancreatitis and viral replication in a non-obese diabetic mouse model. These results illustrate the utility of nAbs for rational design of therapeutics against picornaviruses such as CVB. |
リンク | Cell Host Microbe / PubMed:36002016 |
手法 | EM (単粒子) |
解像度 | 3.02 - 4.18 Å |
構造データ | EMDB-32967, PDB-7x2g: EMDB-32968, PDB-7x2i: EMDB-32969, PDB-7x2o: EMDB-32970, PDB-7x2t: EMDB-32973, PDB-7x2w: EMDB-32979, PDB-7x35: EMDB-32980, PDB-7x37: EMDB-32981, PDB-7x38: EMDB-32983, PDB-7x3c: EMDB-32984, PDB-7x3d: EMDB-32985, PDB-7x3e: EMDB-32986, PDB-7x3f: EMDB-32997, PDB-7x3y: EMDB-32998, PDB-7x40: EMDB-32999, PDB-7x42: EMDB-33000, PDB-7x46: EMDB-33001, PDB-7x47: EMDB-33002, PDB-7x49: EMDB-33003: Cryo-EM structure of Coxsackievirus B1 A-particle in complex with nAb 9A3 (classified from CVB1 mature virion in complex with 8A10 and 9A3) EMDB-33004, PDB-7x4k: EMDB-33005, PDB-7x4m: EMDB-33006: Cryo-EM structure of Coxsackievirus B1 empty particle in complex with nAb 2E6 (classified from CVB1 mature virion in complex with 8A10, 2E6 and 9A3) |
化合物 | ChemComp-PLM: |
由来 |
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キーワード | VIRUS / Coxsackievirus B1 / Neutralizing antiboy / Cryo-EM / Neutralizing antibody |