Cargando…
Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis
The increasing number of SARS-CoV-2 variants associated with highly transmissible phenotypes is a health-public concern in the current pandemic scenario. Herein, we developed a comprehensive in silico analysis of the changes occurring upon mutations in the viral spike. We focused on mutants located...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Leibniz Research Centre for Working Environment and Human Factors
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056063/ https://www.ncbi.nlm.nih.gov/pubmed/33883984 http://dx.doi.org/10.17179/excli2021-3471 |
_version_ | 1783680574809964544 |
---|---|
author | Ortega, Joseph Thomas Pujol, Flor Helene Jastrzebska, Beata Rangel, Hector R. |
author_facet | Ortega, Joseph Thomas Pujol, Flor Helene Jastrzebska, Beata Rangel, Hector R. |
author_sort | Ortega, Joseph Thomas |
collection | PubMed |
description | The increasing number of SARS-CoV-2 variants associated with highly transmissible phenotypes is a health-public concern in the current pandemic scenario. Herein, we developed a comprehensive in silico analysis of the changes occurring upon mutations in the viral spike. We focused on mutants located in the receptor-binding domain of the viral spike protein and analyzed whether these mutants modulate the interaction with the human host receptor angiotensin-converting enzyme II (ACE2). Thirty-two highly prevalent mutants were retrieved from the GISAID database, and their structural models were built using the SWISS-Model server. The stabilization effect for each mutation was assessed by the DUET and DeepDGG software. By applying molecular docking using both Z-Dock and Haddock software we found that multiple mutations, including A475V, V455E, V445L, and V445I, resulted in the higher binding free energy as compared to the wild type (WT) spike protein, thus had a destabilizing effect on the binding to ACE2. On the other hand, several mutants, including the most prevalent N501Y and B.1.1.7 variants, as well as the K444R, L455F, Q493R, and Y505W variants exhibited lower binding free energy as compared to the WT spike. These mutants showed an increased number of electrostatic interactions with ACE2 than the WT spike protein, and they changed the interaction pattern of the neighboring residues. Together, the results presented in this study contribute to a better understanding of the changes in the interaction between SARS-CoV-2 and the human host ACE2 receptor associated with point mutations in the viral spike protein. |
format | Online Article Text |
id | pubmed-8056063 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Leibniz Research Centre for Working Environment and Human Factors |
record_format | MEDLINE/PubMed |
spelling | pubmed-80560632021-04-20 Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis Ortega, Joseph Thomas Pujol, Flor Helene Jastrzebska, Beata Rangel, Hector R. EXCLI J Original Article The increasing number of SARS-CoV-2 variants associated with highly transmissible phenotypes is a health-public concern in the current pandemic scenario. Herein, we developed a comprehensive in silico analysis of the changes occurring upon mutations in the viral spike. We focused on mutants located in the receptor-binding domain of the viral spike protein and analyzed whether these mutants modulate the interaction with the human host receptor angiotensin-converting enzyme II (ACE2). Thirty-two highly prevalent mutants were retrieved from the GISAID database, and their structural models were built using the SWISS-Model server. The stabilization effect for each mutation was assessed by the DUET and DeepDGG software. By applying molecular docking using both Z-Dock and Haddock software we found that multiple mutations, including A475V, V455E, V445L, and V445I, resulted in the higher binding free energy as compared to the wild type (WT) spike protein, thus had a destabilizing effect on the binding to ACE2. On the other hand, several mutants, including the most prevalent N501Y and B.1.1.7 variants, as well as the K444R, L455F, Q493R, and Y505W variants exhibited lower binding free energy as compared to the WT spike. These mutants showed an increased number of electrostatic interactions with ACE2 than the WT spike protein, and they changed the interaction pattern of the neighboring residues. Together, the results presented in this study contribute to a better understanding of the changes in the interaction between SARS-CoV-2 and the human host ACE2 receptor associated with point mutations in the viral spike protein. Leibniz Research Centre for Working Environment and Human Factors 2021-03-08 /pmc/articles/PMC8056063/ /pubmed/33883984 http://dx.doi.org/10.17179/excli2021-3471 Text en Copyright © 2021 Ortega et al. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ) You are free to copy, distribute and transmit the work, provided the original author and source are credited. |
spellingShingle | Original Article Ortega, Joseph Thomas Pujol, Flor Helene Jastrzebska, Beata Rangel, Hector R. Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title | Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title_full | Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title_fullStr | Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title_full_unstemmed | Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title_short | Mutations in the SARS-CoV-2 spike protein modulate the virus affinity to the human ACE2 receptor, an in silico analysis |
title_sort | mutations in the sars-cov-2 spike protein modulate the virus affinity to the human ace2 receptor, an in silico analysis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056063/ https://www.ncbi.nlm.nih.gov/pubmed/33883984 http://dx.doi.org/10.17179/excli2021-3471 |
work_keys_str_mv | AT ortegajosephthomas mutationsinthesarscov2spikeproteinmodulatethevirusaffinitytothehumanace2receptoraninsilicoanalysis AT pujolflorhelene mutationsinthesarscov2spikeproteinmodulatethevirusaffinitytothehumanace2receptoraninsilicoanalysis AT jastrzebskabeata mutationsinthesarscov2spikeproteinmodulatethevirusaffinitytothehumanace2receptoraninsilicoanalysis AT rangelhectorr mutationsinthesarscov2spikeproteinmodulatethevirusaffinitytothehumanace2receptoraninsilicoanalysis |