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A broadly neutralizing humanized ACE2-targeting antibody against SARS-CoV-2 variants.
Du, Yanyun; Shi, Rui; Zhang, Ying; Duan, Xiaomin; Li, Li; Zhang, Jing; Wang, Fengze; Zhang, Ruixue; Shen, Hao; Wang, Yue; Wu, Zheng; Peng, Qianwen; Pan, Ting; Sun, Wanwei; Huang, Weijin; Feng, Yue; Feng, Hui; Xiao, Junyu; Tan, Wenjie; Wang, Youchun; Wang, Chenhui; Yan, Jinghua.
  • Du Y; 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.
  • Shi R; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Zhang Y; 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.
  • Duan X; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Li L; University of Chinese Academy of Sciences, Beijing, China.
  • Zhang J; Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.
  • Wang F; Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.
  • Zhang R; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Shen H; University of Chinese Academy of Sciences, Beijing, China.
  • Wang Y; 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.
  • Wu Z; 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.
  • Peng Q; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Pan T; University of Chinese Academy of Sciences, Beijing, China.
  • Sun W; CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Huang W; Institute of Physical Science and Information, Anhui University, Hefei, China.
  • Feng Y; 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.
  • Feng H; 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.
  • Xiao J; 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.
  • Tan W; 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.
  • Wang Y; 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.
  • Wang C; Shanghai Junshi Biosciences Co., Ltd, Shanghai, China.
  • Yan J; 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.
Nat Commun ; 12(1): 5000, 2021 08 17.
Article in English | MEDLINE | ID: covidwho-1361637
ABSTRACT
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Animals / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25331-x

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / Angiotensin-Converting Enzyme 2 / SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Prognostic study Topics: Variants Limits: Animals / Female / Humans / Male Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-25331-x