一种针对SARS-CoV-2 变体的广泛中和人源化ACE2 靶向抗体 - X-MOL

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搜索当前位置： X-MOL 学术 › Nat. Commun. › 论文详情 Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.) A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants Nature Communications ( IF 15.7 ) Pub Date : 2021-08-17 , DOI: 10.1038/s41467-021-25331-x Yanyun Du

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

, Rui Shi

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

, Ying Zhang

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.

, Xiaomin Duan

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

, Li Li

Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.

, Jing Zhang

Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.

, Fengze Wang

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

, Ruixue Zhang

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.

, Hao Shen

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.

, Yue Wang

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

, Zheng Wu

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Institute of Physical Science and Information, Anhui University, Hefei, China.

, Qianwen Peng

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

, Ting Pan

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

, Wanwei Sun

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

, Weijin Huang

Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.

, Yue Feng

Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Key Laboratory of Bioprocess, State Key Laboratory of Chemical Resource Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.

, Hui Feng

Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.

, Junyu Xiao

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Beijing Advanced Innovation Center for Genomics, Peking University, Beijing, China.

, Wenjie Tan

NHC Key Laboratory of Biosafety, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.

, Youchun Wang

Division of HIV/AIDS and Sex-transmitted Virus Vaccines, Institute for Biological Product Control, National Institutes for Food and Drug Control (NIFDC) and WHO Collaborating Center for Standardization and Evaluation of Biologicals, Beijing, China.

, Chenhui Wang

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.

, Jinghua Yan

CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.

The successive emergences and accelerating spread of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages and evolved resistance to some ongoing clinical therapeutics increase the risks associated with the coronavirus disease 2019 (COVID-19) pandemic. An urgent intervention for broadly effective therapies to limit the morbidity and mortality of COVID-19 and future transmission events from SARS-related coronaviruses (SARSr-CoVs) is needed. Here, we isolate and humanize an angiotensin-converting enzyme-2 (ACE2)-blocking monoclonal antibody (MAb), named h11B11, which exhibits potent inhibitory activity against SARS-CoV and circulating global SARS-CoV-2 lineages. When administered therapeutically or prophylactically in the hACE2 mouse model, h11B11 alleviates and prevents SARS-CoV-2 replication and virus-induced pathological syndromes. No significant changes in blood pressure and hematology chemistry toxicology were observed after injections of multiple high dosages of h11B11 in cynomolgus monkeys. Analysis of the structures of the h11B11/ACE2 and receptor-binding domain (RBD)/ACE2 complexes shows hindrance and epitope competition of the MAb and RBD for the receptor. Together, these results suggest h11B11 as a potential therapeutic countermeasure against SARS-CoV, SARS-CoV-2, and escape variants.

中文翻译：

一种针对 SARS-CoV-2 变体的广泛中和人源化 ACE2 靶向抗体

新型严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 谱系的连续出现和加速传播以及对某些正在进行的临床治疗的进化耐药性增加了与 2019 年冠状病毒病 (COVID-19) 大流行相关的风险。需要对广泛有效的疗法进行紧急干预，以限制 COVID-19 的发病率和死亡率以及未来 SARS 相关冠状病毒 (SARSr-CoV) 的传播事件。在这里，我们分离并人源化了一种名为 h11B11 的血管紧张素转化酶 2 (ACE2) 阻断单克隆抗体 (MAb)，该抗体对 SARS-CoV 和循环全球 SARS-CoV-2 谱系具有有效的抑制活性。当在 hACE2 小鼠模型中进行治疗性或预防性给药时，h11B11 减轻和预防 SARS-CoV-2 复制和病毒引起的病理综合征。在食蟹猴中注射多次高剂量的 h11B11 后，未观察到血压和血液化学毒理学的显着变化。h11B11/ACE2 和受体结合域 (RBD)/ACE2 复合物的结构分析显示 MAb 和 RBD 对受体的阻碍和表位竞争。总之，这些结果表明 h11B11 是针对 SARS-CoV、SARS-CoV-2 和逃逸变体的潜在治疗对策。h11B11/ACE2 和受体结合域 (RBD)/ACE2 复合物的结构分析显示 MAb 和 RBD 对受体的阻碍和表位竞争。总之，这些结果表明 h11B11 是针对 SARS-CoV、SARS-CoV-2 和逃逸变体的潜在治疗对策。h11B11/ACE2 和受体结合域 (RBD)/ACE2 复合物的结构分析显示 MAb 和 RBD 对受体的阻碍和表位竞争。总之，这些结果表明 h11B11 是针对 SARS-CoV、SARS-CoV-2 和逃逸变体的潜在治疗对策。