Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784604908000903168
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
work_keys_str_mv AT khanabbas structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT mohammadanwar structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT haqinamul structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT nasarmohammad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT ahmadwaqar structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT yousafiqudsia structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT sulemanmuhammad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT ahmadsajjad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT albuttiaqel structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT khantaimoor structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT marafiesulaimank structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT alshawafeman structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT alisyedshujait structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT abubakerjehad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
AT weidongqing structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity