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Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Published by Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020654/ https://www.ncbi.nlm.nih.gov/pubmed/35460753 http://dx.doi.org/10.1016/j.ijbiomac.2022.04.096 |
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author | 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 |
author_facet | 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 |
author_sort | Li, Tingting |
collection | PubMed |
description | 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-9020654 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90206542022-04-21 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 Int J Biol Macromol Article 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 IC(50) 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. Published by Elsevier B.V. 2022-06-01 2022-04-20 /pmc/articles/PMC9020654/ /pubmed/35460753 http://dx.doi.org/10.1016/j.ijbiomac.2022.04.096 Text en © 2022 Published by Elsevier B.V. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article 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 Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title | Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title_full | Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title_fullStr | Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title_full_unstemmed | Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title_short | Isolation, characterization, and structure-based engineering of a neutralizing nanobody against SARS-CoV-2 |
title_sort | isolation, characterization, and structure-based engineering of a neutralizing nanobody against sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020654/ https://www.ncbi.nlm.nih.gov/pubmed/35460753 http://dx.doi.org/10.1016/j.ijbiomac.2022.04.096 |
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