A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.
A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein.
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DOI：
10.1038/s41467-020-20602-5
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发表时间：
2021-01-12
影响因子：
16.6
通讯作者：
Lee SY
中科院分区：
文献类型：
--
作者：
Kim C;Ryu DK;Lee J;Kim YI;Seo JM;Kim YG;Jeong JH;Kim M;Kim JI;Kim P;Bae JS;Shim EY;Lee MS;Kim MS;Noh H;Park GS;Park JS;Son D;An Y;Lee JN;Kwon KS;Lee JY;Lee H;Yang JS;Kim KC;Kim SS;Woo HM;Kim JW;Park MS;Yu KM;Kim SM;Kim EH;Park SJ;Jeong ST;Yu CH;Song Y;Gu SH;Oh H;Koo BS;Hong JJ;Ryu CM;Park WB;Oh MD;Choi YK;Lee SY
严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）引起的大流行急需疫苗和治疗药物。在这里，我们筛选人单克隆抗体（mAb）靶向的受体结合结构域（RBD）的病毒刺突蛋白通过抗体库从外周血单个核细胞的康复期患者。CT-P59 mAb可有效中和SARS-CoV-2分离株，包括D 614 G变体，无抗体依赖性增强效应。CT-P59 Fab/RBD的复杂晶体结构表明，CT-P59阻断RBD与血管紧张素转换酶2（ACE 2）受体的相互作用区域，其取向与先前报道的RBD靶向mAb明显不同。此外，在三种动物模型（雪貂、仓鼠和恒河猴）中评价了CT-P59的治疗效果，证明病毒滴度沿着临床症状的缓解显著降低。因此，CT-P59可能是COVID-19的有希望的治疗候选物。由SARS-CoV-2病毒大流行引起的COVID-19的治疗和疫苗是迫切需要的。在本文中，作者从恢复期COVID-19患者中建立并筛选了一个抗体库，以分离出一种中和抗体，该抗体能够在雪貂、仓鼠和恒河猴感染模型中降低病毒滴度并缓解症状。
Vaccines and therapeutics are urgently needed for the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we screen human monoclonal antibodies (mAb) targeting the receptor binding domain (RBD) of the viral spike protein via antibody library constructed from peripheral blood mononuclear cells of a convalescent patient. The CT-P59 mAb potently neutralizes SARS-CoV-2 isolates including the D614G variant without antibody-dependent enhancement effect. Complex crystal structure of CT-P59 Fab/RBD shows that CT-P59 blocks interaction regions of RBD for angiotensin converting enzyme 2 (ACE2) receptor with an orientation that is notably different from previously reported RBD-targeting mAbs. Furthermore, therapeutic effects of CT-P59 are evaluated in three animal models (ferret, hamster, and rhesus monkey), demonstrating a substantial reduction in viral titer along with alleviation of clinical symptoms. Therefore, CT-P59 may be a promising therapeutic candidate for COVID-19. Therapies and vaccines for COVID-19, caused by the SARS-CoV-2 viral pandemic, are urgently needed. Here the authors establish and screen an antibody library from a convalescent COVID-19 patient to isolate a neutralizing antibody with the ability to reduce viral titer and alleviate symptoms in ferret, hamster, and rhesus monkey infection models.
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DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
56.9
作者：
Lv, Zhe;Deng, Yong-Qiang;Wang, Xiangxi
通讯作者：
Wang, Xiangxi
影响因子：
120.7
作者：
Li, Ling;Zhang, Wei;Liu, Zhong
通讯作者：
Liu, Zhong
影响因子：
5.4
作者：
Jaume, Martial;Yip, Ming S.;Peiris, J. S. Malik
通讯作者：
Peiris, J. S. Malik
DOI：
10.1107/s0907444909052925
发表时间：
2010-02
期刊：
Acta crystallographica. Section D, Biological crystallography
影响因子：
--
作者：
Adams PD;Afonine PV;Bunkóczi G;Chen VB;Davis IW;Echols N;Headd JJ;Hung LW;Kapral GJ;Grosse-Kunstleve RW;McCoy AJ;Moriarty NW;Oeffner R;Read RJ;Richardson DC;Richardson JS;Terwilliger TC;Zwart PH
通讯作者：
Zwart PH