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Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants
The global spread of COVID-19 is devastating health systems and economies worldwide. While the use of vaccines has yielded encouraging results, the emergence of new variants of SARS-CoV-2 shows that combating COVID-19 remains a big challenge. One of the most promising treatments is the use of not on...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188278/ https://www.ncbi.nlm.nih.gov/pubmed/35690632 http://dx.doi.org/10.1038/s41598-022-14263-1 |
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author | Nguyen, Hung Li, Mai Suan |
author_facet | Nguyen, Hung Li, Mai Suan |
author_sort | Nguyen, Hung |
collection | PubMed |
description | The global spread of COVID-19 is devastating health systems and economies worldwide. While the use of vaccines has yielded encouraging results, the emergence of new variants of SARS-CoV-2 shows that combating COVID-19 remains a big challenge. One of the most promising treatments is the use of not only antibodies, but also nanobodies. Recent experimental studies revealed that the combination of antibody and nanobody can significantly improve their neutralizing ability through binding to the SARS-CoV-2 spike protein, but the molecular mechanisms underlying this observation remain largely unknown. In this work, we investigated the binding affinity of the CR3022 antibody and H11-H4 nanobody to the SARS-CoV-2 receptor binding domain (RBD) using molecular modeling. Both all-atom steered molecular dynamics simulations and coarse-grained umbrella sampling showed that, consistent with the experiment, CR3022 associates with RBD more strongly than H11-H4. We predict that the combination of CR3022 and H11-H4 considerably increases their binding affinity to the spike protein. The electrostatic interaction was found to control the association strength of CR3022, but the van der Waals interaction dominates in the case of H11-H4. However, our study for a larger set of nanobodies and antibodies showed that the relative role of these interactions depends on the specific complex. Importantly, we showed Beta, Gamma, Lambda, and Mu variants reduce the H11-H4 activity while Alpha, Kappa and Delta variants increase its neutralizing ability, which is in line with experiment reporting that the nanobody elicited from the llama is very promising for fighting against the Delta variant. |
format | Online Article Text |
id | pubmed-9188278 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91882782022-06-13 Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants Nguyen, Hung Li, Mai Suan Sci Rep Article The global spread of COVID-19 is devastating health systems and economies worldwide. While the use of vaccines has yielded encouraging results, the emergence of new variants of SARS-CoV-2 shows that combating COVID-19 remains a big challenge. One of the most promising treatments is the use of not only antibodies, but also nanobodies. Recent experimental studies revealed that the combination of antibody and nanobody can significantly improve their neutralizing ability through binding to the SARS-CoV-2 spike protein, but the molecular mechanisms underlying this observation remain largely unknown. In this work, we investigated the binding affinity of the CR3022 antibody and H11-H4 nanobody to the SARS-CoV-2 receptor binding domain (RBD) using molecular modeling. Both all-atom steered molecular dynamics simulations and coarse-grained umbrella sampling showed that, consistent with the experiment, CR3022 associates with RBD more strongly than H11-H4. We predict that the combination of CR3022 and H11-H4 considerably increases their binding affinity to the spike protein. The electrostatic interaction was found to control the association strength of CR3022, but the van der Waals interaction dominates in the case of H11-H4. However, our study for a larger set of nanobodies and antibodies showed that the relative role of these interactions depends on the specific complex. Importantly, we showed Beta, Gamma, Lambda, and Mu variants reduce the H11-H4 activity while Alpha, Kappa and Delta variants increase its neutralizing ability, which is in line with experiment reporting that the nanobody elicited from the llama is very promising for fighting against the Delta variant. Nature Publishing Group UK 2022-06-11 /pmc/articles/PMC9188278/ /pubmed/35690632 http://dx.doi.org/10.1038/s41598-022-14263-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Nguyen, Hung Li, Mai Suan Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title | Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title_full | Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title_fullStr | Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title_full_unstemmed | Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title_short | Antibody–nanobody combination increases their neutralizing activity against SARS-CoV-2 and nanobody H11-H4 is effective against Alpha, Kappa and Delta variants |
title_sort | antibody–nanobody combination increases their neutralizing activity against sars-cov-2 and nanobody h11-h4 is effective against alpha, kappa and delta variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188278/ https://www.ncbi.nlm.nih.gov/pubmed/35690632 http://dx.doi.org/10.1038/s41598-022-14263-1 |
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