Identification and characterization of a monoclonal antibody blocking the SARS-CoV-2 spike protein-ACE2 interaction.

Identification and characterization of a monoclonal antibody blocking the SARS-CoV-2 spike protein-ACE2 interaction.
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阻断SARS-CoV-2刺突蛋白- ace2相互作用的单克隆抗体的鉴定和鉴定

DOI:
10.1038/s41423-021-00684-x
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发表时间:
2021-06
影响因子:
24.1
通讯作者:
Chen J
Chen J
中科院分区:
医学1区
文献类型:
--
作者:
Yuan M;Wan Y;Liu C;Li Y;Liu Z;Lin C;Chen J

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2019冠状病毒病(COVID-19)是由严重急性呼吸道综合征冠状病毒2(SARS-CoV-2)感染引起的急性肺炎。根据约翰霍普金斯大学于2021年4月6日发布的COVID-19最新统计数据,全球确诊病例为1. 3245亿例,死亡病例为287万例。由于COVID-19已成为全球性大流行病,因此迫切需要开发针对这种疾病的治疗方法,例如能够有效阻断SARS-CoV-2感染的中和抗体。在SARS-CoV-2感染宿主细胞的过程中,SARS-CoV-2的S糖蛋白在病毒进入和细胞融合中起着最关键的作用。S蛋白包括两个组分,S1和S2亚基。S1亚基在决定组织嗜性和宿主范围方面至关重要,由N-末端结构域和C-末端受体结合结构域(RBD)组成。1,2值得注意的是,S蛋白的RBD(S-RBD)支持S蛋白与宿主细胞上的血管紧张素转换酶2(ACE 2)结合,有助于SARS-CoV-2进入细胞。因此,S-RBD被广泛用于中和抗体、小分子抑制剂和疫苗的开发。4先前的研究已经报道了几种针对S-RBD的中和抗体,这些抗体是从恢复期COVID-19患者、用SARS-CoV-2 S蛋白免疫的转基因小鼠或美洲驼中鉴定的,并发现它们抑制S蛋白和ACE 2之间的相互作用。5-7除了从患者和免疫动物中分离抗体之外,工程化单克隆抗体(mAb)文库还提供了用于筛选治疗性mAb的强大工具,具有安全性、易于执行和高效的优点。8
Coronavirus disease 2019 (COVID-19) is an acute pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the latest statistics for COVID-19 released by Johns Hopkins University on April 6, 2021, there were 132.45 million confirmed cases and 2.87 million deaths globally. Because COVID-19 has spread as a global pandemic, the development of therapeutics for this disease, such as neutralizing antibodies that can efficiently block SARS-CoV-2 infection, is urgently needed.During the infection of host cells by SARS-CoV-2, the spike (S) glycoprotein of SARS-CoV-2 plays the most crucial roles in viral entry and cell fusion. The S protein includes two components, the S1 and S2 subunits. The S1 subunit is vital in determining tissue tropism and host ranges and consists of the N-terminal domain and C-terminal receptor-binding domain (RBD). 1, 2 Of note, the RBD of the S protein (S-RBD) supports the binding of the S protein to angiotensin-converting enzyme 2 (ACE2) on host cells, contributing to cell entry by SARS-CoV-2. 3 Therefore, the S-RBD is widely used for the development of neutralizing antibodies, smallmolecule inhibitors and vaccines. 4 Previous studies have reported several neutralizing antibodies against the S-RBD that were identified from convalescent COVID-19 patients, transgenic mice or llamas immunized with the SARS-CoV-2 S protein and found to inhibit the interaction between the S protein and ACE2. 5–7 In addition to isolating antibodies from patients and immunized animals, an engineered monoclonal antibody (mAb) library provides a powerful tool for screening therapeutic mAbs, with the advantages of safety, ease of performance and high efficiency. 8
DOI: 10.1038/s41467-020-19813-7
发表时间: 2020-12-08
影响因子: 16.6
作者:
Wang C;Li H;Guo Y;Huang J;Sun Y;Min J;Wang J;Fang X;Zhao Z;Wang S;Zhang Y;Liu Q;Jiang Q;Wang X;Guo Y;Yang C;Wang Y;Tian F;Zhuang G;Fan Y;Gao Q;Li Y;Ju Z;Li J;Li R;Hou M;Yang G;Liu G;Liu W;Guo J;Pan S;Fan G;Zhang W;Zhang R;Yu J;Zhang X;Yin Q;Ji C;Jin Y;Yue G;Liu M;Xu J;Liu S;Jordana J;Noce A;Amills M;Wu DD;Li S;Zhou X;Zhong J
通讯作者: Zhong J
DOI: 10.1126/sciimmunol.abc8413
发表时间: 2020-06-01
期刊: SCIENCE IMMUNOLOGY
影响因子: 24.8
作者:
Premkumar, Lakshmanane;Segovia-Chumbez, Bruno;de Silva, Aravinda M.
通讯作者: de Silva, Aravinda M.
DOI: 10.1016/j.cell.2020.04.031
发表时间: 2020-05-28
期刊: CELL
影响因子: 64.5
作者:
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DOI: 10.1016/j.cell.2020.02.058
发表时间: 2020-04-16
期刊: CELL
影响因子: 64.5
作者:
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通讯作者: Veesler, David
DOI: 10.1038/s41586-020-2381-y
发表时间: 2020-05-26
期刊: NATURE
影响因子: 64.8
作者:
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通讯作者: Yan, Jinghua