机构：[1]Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China[2]Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai, China[3]Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, China[4]Institute of Biomedicine, Jinan University, Guangzhou, China[5]Department of Infectious Diseases, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China[6]Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Taipa, Macau, China[7]School of Health Sciences and Sports, Macao Polytechnic Institute, Macao, China
The emerging new lineages of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have marked a new phase of coronavirus disease 2019 (COVID-19). Understanding the recognition mechanisms of potent neutralizing monoclonal antibodies (NAbs) against the spike protein is pivotal for developing new vaccines and antibody drugs. Here, we isolated several monoclonal antibodies (MAbs) against the SARS-CoV-2 spike protein receptor-binding domain (S-RBD) from the B cell receptor repertoires of a SARS-CoV-2 convalescent. Among these MAbs, the antibody nCoV617 demonstrates the most potent neutralizing activity against authentic SARS-CoV-2 infection, as well as prophylactic and therapeutic efficacies against the human angiotensin-converting enzyme 2 (ACE2) transgenic mouse model in vivo. The crystal structure of S-RBD in complex with nCoV617 reveals that nCoV617 mainly binds to the back of the "ridge" of RBD and shares limited binding residues with ACE2. Under the background of the S-trimer model, it potentially binds to both "up" and "down" conformations of S-RBD. In vitro mutagenesis assays show that mutant residues found in the emerging new lineage B.1.1.7 of SARS-CoV-2 do not affect nCoV617 binding to the S-RBD. These results provide a new human-sourced neutralizing antibody against the S-RBD and assist vaccine development. IMPORTANCE COVID-19 is a respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 pandemic has posed a serious threat to global health and the economy, so it is necessary to find safe and effective antibody drugs and treatments. The receptor-binding domain (RBD) in the SARS-CoV-2 spike protein is responsible for binding to the angiotensin-converting enzyme 2 (ACE2) receptor. It contains a variety of dominant neutralizing epitopes and is an important antigen for the development of new coronavirus antibodies. The significance of our research lies in the determination of new epitopes, the discovery of antibodies against RBD, and the evaluation of the antibodies' neutralizing effect. The identified antibodies here may be drug candidates for the development of clinical interventions for SARS-CoV-2.
基金：
National Natural Science Foundation of China (grant
number 32171192, 31770801) to S.C., the Natural Science Foundation of Guangdong Province,
China (2018B030306029) to S.C., COVID-19 Emerging Prevention Products, Research Special
Fund of Zhuhai City (ZH22036302200016PWC to S.C., ZH22046301200011PWC to H.-X.L., and
ZH22046301200011PWC to H.-X.L. and S.C.), and the Zhuhai Innovative and Entrepreneurial
Research Team Program (ZH01110405160015PWC and ZH01110405180040PWC,) to H.-X.L.
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类|2 区生物
小类|2 区微生物学
最新[2025]版：
大类|2 区生物学
小类|3 区微生物学
第一作者：
第一作者机构：[1]Molecular Imaging Center, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China
共同第一作者：
通讯作者：
通讯机构：[2]Zhuhai Trinomab Biotechnology Co., Ltd., Zhuhai, China[4]Institute of Biomedicine, Jinan University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Yang Mei,Li Jiaqi,Huang Zhaoxia,et al.Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.[J].Microbiology spectrum.2021,9(2):e0135221.doi:10.1128/Spectrum.01352-21.
APA：
Yang Mei,Li Jiaqi,Huang Zhaoxia,Li Heng,Wang Yueming...&Chen Shoudeng.(2021).Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain..Microbiology spectrum,9,(2)
MLA：
Yang Mei,et al."Structural Basis of a Human Neutralizing Antibody Specific to the SARS-CoV-2 Spike Protein Receptor-Binding Domain.".Microbiology spectrum 9..2(2021):e0135221
