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Structural basis for SARS-CoV-2 neutralizing antibodies with novel binding epitopes.
Fu, Dan; Zhang, Guangshun; Wang, Yuhui; Zhang, Zheng; Hu, Hengrui; Shen, Shu; Wu, Jun; Li, Bo; Li, Xin; Fang, Yaohui; Liu, Jia; Wang, Qiao; Zhou, Yunjiao; Wang, Wei; Li, Yufeng; Lu, Zhonghua; Wang, Xiaoxiao; Nie, Cui; Tian, Yujie; Chen, Da; Wang, Yuan; Zhou, Xingdong; Wang, Qisheng; Yu, Feng; Zhang, Chen; Deng, Changjing; Zhou, Liang; Guan, Guangkuo; Shao, Na; Lou, Zhiyong; Deng, Fei; Zhang, Hongkai; Chen, Xinwen; Wang, Manli; Liu, Louis; Rao, Zihe; Guo, Yu.
  • Fu D; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Zhang G; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Wang Y; Harbour Biomed (Suzhou) Co. Ltd., Suzhou Industrial Park, Suzhou, China.
  • Zhang Z; College of Life Science, Nankai University, Tianjin, China.
  • Hu H; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Shen S; College of Life Science, Nankai University, Tianjin, China.
  • Wu J; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Li B; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Li X; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
  • Fang Y; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Liu J; State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Wang Q; Harbour Biomed (Suzhou) Co. Ltd., Suzhou Industrial Park, Suzhou, China.
  • Zhou Y; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Wang W; College of Life Science, Nankai University, Tianjin, China.
  • Li Y; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Lu Z; College of Life Science, Nankai University, Tianjin, China.
  • Wang X; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
  • Nie C; State Key Laboratory of Virology and National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Tian Y; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Chen D; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Wang Y; Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
  • Zhou X; Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.
  • Wang Q; Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China.
  • Yu F; Harbour Biomed (Suzhou) Co. Ltd., Suzhou Industrial Park, Suzhou, China.
  • Zhang C; Harbour Biomed (Suzhou) Co. Ltd., Suzhou Industrial Park, Suzhou, China.
  • Deng C; Harbour Biomed (Suzhou) Co. Ltd., Suzhou Industrial Park, Suzhou, China.
  • Zhou L; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Guan G; Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
  • Shao N; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Lou Z; College of Life Science, Nankai University, Tianjin, China.
  • Deng F; Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
  • Zhang H; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Chen X; College of Life Science, Nankai University, Tianjin, China.
  • Wang M; Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
  • Liu L; State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
  • Rao Z; College of Life Science, Nankai University, Tianjin, China.
  • Guo Y; Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
PLoS Biol ; 19(5): e3001209, 2021 05.
Article in English | MEDLINE | ID: covidwho-1219261
ABSTRACT
The ongoing Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) threatens global public health and economy unprecedentedly, requiring accelerating development of prophylactic and therapeutic interventions. Molecular understanding of neutralizing antibodies (NAbs) would greatly help advance the development of monoclonal antibody (mAb) therapy, as well as the design of next generation recombinant vaccines. Here, we applied H2L2 transgenic mice encoding the human immunoglobulin variable regions, together with a state-of-the-art antibody discovery platform to immunize and isolate NAbs. From a large panel of isolated antibodies, 25 antibodies showed potent neutralizing activities at sub-nanomolar levels by engaging the spike receptor-binding domain (RBD). Importantly, one human NAb, termed PR1077, from the H2L2 platform and 2 humanized NAb, including PR953 and PR961, were further characterized and subjected for subsequent structural analysis. High-resolution X-ray crystallography structures unveiled novel epitopes on the receptor-binding motif (RBM) for PR1077 and PR953, which directly compete with human angiotensin-converting enzyme 2 (hACE2) for binding, and a novel non-blocking epitope on the neighboring site near RBM for PR961. Moreover, we further tested the antiviral efficiency of PR1077 in the Ad5-hACE2 transduction mouse model of COVID-19. A single injection provided potent protection against SARS-CoV-2 infection in either prophylactic or treatment groups. Taken together, these results shed light on the development of mAb-related therapeutic interventions for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: PLoS Biol Journal subject: Biology Year: 2021 Document Type: Article Affiliation country: Journal.pbio.3001209

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Antibodies, Neutralizing / SARS-CoV-2 / COVID-19 Type of study: Experimental Studies / Observational study / Randomized controlled trials Topics: Vaccines Limits: Animals / Humans Language: English Journal: PLoS Biol Journal subject: Biology Year: 2021 Document Type: Article Affiliation country: Journal.pbio.3001209