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Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity
Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619099/ https://www.ncbi.nlm.nih.gov/pubmed/34835456 http://dx.doi.org/10.3390/microorganisms9112331 |
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author | Khan, Abbas Mohammad, Anwar Haq, Inamul Nasar, Mohammad Ahmad, Waqar Yousafi, Qudsia Suleman, Muhammad Ahmad, Sajjad Albutti, Aqel Khan, Taimoor Marafie, Sulaiman K. Alshawaf, Eman Ali, Syed Shujait Abubaker, Jehad Wei, Dong-Qing |
author_facet | Khan, Abbas Mohammad, Anwar Haq, Inamul Nasar, Mohammad Ahmad, Waqar Yousafi, Qudsia Suleman, Muhammad Ahmad, Sajjad Albutti, Aqel Khan, Taimoor Marafie, Sulaiman K. Alshawaf, Eman Ali, Syed Shujait Abubaker, Jehad Wei, Dong-Qing |
author_sort | Khan, Abbas |
collection | PubMed |
description | Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness. |
format | Online Article Text |
id | pubmed-8619099 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86190992021-11-27 Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity Khan, Abbas Mohammad, Anwar Haq, Inamul Nasar, Mohammad Ahmad, Waqar Yousafi, Qudsia Suleman, Muhammad Ahmad, Sajjad Albutti, Aqel Khan, Taimoor Marafie, Sulaiman K. Alshawaf, Eman Ali, Syed Shujait Abubaker, Jehad Wei, Dong-Qing Microorganisms Article Glucose-regulated protein 78 (GRP78) might be a receptor for SARS-CoV-2 to bind and enter the host cell. Recently reported mutations in the spike glycoprotein unique to the receptor-binding domain (RBD) of different variants might increase the binding and pathogenesis. However, it is still not known how these mutations affect the binding of RBD to GRP78. The current study provides a structural basis for the binding of GRP78 to the different variants, i.e., B.1.1.7, B.1.351, B.1.617, and P.1 (spike RBD), of SARS-CoV-2 using a biomolecular simulation approach. Docking results showed that the new variants bound stronger than the wild-type, which was further confirmed through the free energy calculation results. All-atom simulation confirmed structural stability, which was consistent with previous results by following the global stability trend. We concluded that the increased binding affinity of the B.1.1.7, B.1.351, and P.1 variants was due to a variation in the bonding network that helped the virus induce a higher infectivity and disease severity. Consequently, we reported that the aforementioned new variants use GRP78 as an alternate receptor to enhance their seriousness. MDPI 2021-11-11 /pmc/articles/PMC8619099/ /pubmed/34835456 http://dx.doi.org/10.3390/microorganisms9112331 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Khan, Abbas Mohammad, Anwar Haq, Inamul Nasar, Mohammad Ahmad, Waqar Yousafi, Qudsia Suleman, Muhammad Ahmad, Sajjad Albutti, Aqel Khan, Taimoor Marafie, Sulaiman K. Alshawaf, Eman Ali, Syed Shujait Abubaker, Jehad Wei, Dong-Qing Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title | Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title_full | Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title_fullStr | Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title_full_unstemmed | Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title_short | Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity |
title_sort | structural-dynamics and binding analysis of rbd from sars-cov-2 variants of concern (vocs) and grp78 receptor revealed basis for higher infectivity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619099/ https://www.ncbi.nlm.nih.gov/pubmed/34835456 http://dx.doi.org/10.3390/microorganisms9112331 |
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