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Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2.
Li, Tingting; Zhou, Bingjie; Li, Yaning; Huang, Suqiong; Luo, Zhipu; Zhou, Yuanze; Lai, Yanling; Gautam, Anupriya; Bourgeau, Salome; Wang, Shurui; Bao, Juan; Tan, Jingquan; Lavillette, Dimitri; Li, Dianfan.
Afiliación
  • Li T; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200030, China.
  • Zhou B; University of CAS, Beijing 101408, China; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai CAS, 320 Yueyang Road, Shanghai 200031, China.
  • Li Y; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200030, China; University of CAS, Beijing 101408, China.
  • Huang S; University of CAS, Beijing 101408, China; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai CAS, 320 Yueyang Road, Shanghai 200031, China; College of Pharmacy, Chongqing Medical University, China.
  • Luo Z; Institute of Molecular Enzymology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
  • Zhou Y; Nanjing Crycision Biotech Co., Ltd., Nanjing, China.
  • Lai Y; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200030, China; University of CAS, Beijing 101408, China.
  • Gautam A; University of CAS, Beijing 101408, China; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai CAS, 320 Yueyang Road, Shanghai 200031, China.
  • Bourgeau S; University of CAS, Beijing 101408, China; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai CAS, 320 Yueyang Road, Shanghai 200031, China; Institut National de la Santé et de la Recherche Médicale, École des Hautes Etudes en Santé Publique, Institut de Recherche
  • Wang S; Nanjing Crycision Biotech Co., Ltd., Nanjing, China.
  • Bao J; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200030, China.
  • Tan J; Nanjing Crycision Biotech Co., Ltd., Nanjing, China.
  • Lavillette D; CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai CAS, 320 Yueyang Road, Shanghai 200031, China; Pasteurien College, Soochow University, Jiangsu, China. Electronic address: dlaville@ips.ac.cn.
  • Li D; State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences (CAS), 320 Yueyang Road, Shanghai 200030, China. Electronic address: dianfan.li@sibcb.ac.cn.
Int J Biol Macromol ; 209(Pt A): 1379-1388, 2022 Jun 01.
Article en En | MEDLINE | ID: mdl-35460753
SARS-CoV-2 engages with human cells through the binding of its Spike receptor-binding domain (S-RBD) to the receptor ACE2. Molecular blocking of this engagement represents a proven strategy to treat COVID-19. Here, we report a single-chain antibody (nanobody, DL4) isolated from immunized alpaca with picomolar affinity to RBD. DL4 neutralizes SARS-CoV-2 pseudoviruses with an IC50 of 0.101 µg mL-1 (6.2 nM). A crystal structure of the DL4-RBD complex at 1.75-Å resolution unveils the interaction detail and reveals a direct competition mechanism for DL4's ACE2-blocking and hence neutralizing activity. The structural information allows us to rationally design a mutant with higher potency. Our work adds diversity of neutralizing nanobodies against SARS-CoV-2 and should encourage protein engineering to improve antibody affinities in general.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos de Dominio Único / SARS-CoV-2 Idioma: En Revista: Int J Biol Macromol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
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PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Anticuerpos de Dominio Único / SARS-CoV-2 Idioma: En Revista: Int J Biol Macromol Año: 2022 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos