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

Guardado en:

Detalles Bibliográficos
Autores principales:	Abbas Khan, Anwar Mohammad, Inamul Haq, Mohammad Nasar, Waqar Ahmad, Qudsia Yousafi, Muhammad Suleman, Sajjad Ahmad, Aqel Albutti, Taimoor Khan, Sulaiman K. Marafie, Eman Alshawaf, Syed Shujait Ali, Jehad Abubaker, Dong-Qing Wei
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	COVID-19 SARS-CoV-2 new variants GRP78 infectivity Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/eca055d1a3644e9792cfcca8455fd873
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eca055d1a3644e9792cfcca8455fd873
record_format	dspace
spelling	oai:doaj.org-article:eca055d1a3644e9792cfcca8455fd8732021-11-25T18:25:11ZStructural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity10.3390/microorganisms91123312076-2607https://doaj.org/article/eca055d1a3644e9792cfcca8455fd8732021-11-01T00:00:00Zhttps://www.mdpi.com/2076-2607/9/11/2331https://doaj.org/toc/2076-2607Glucose-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.Abbas KhanAnwar MohammadInamul HaqMohammad NasarWaqar AhmadQudsia YousafiMuhammad SulemanSajjad AhmadAqel AlbuttiTaimoor KhanSulaiman K. MarafieEman AlshawafSyed Shujait AliJehad AbubakerDong-Qing WeiMDPI AGarticleCOVID-19SARS-CoV-2new variantsGRP78infectivityBiology (General)QH301-705.5ENMicroorganisms, Vol 9, Iss 2331, p 2331 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 SARS-CoV-2 new variants GRP78 infectivity Biology (General) QH301-705.5
spellingShingle	COVID-19 SARS-CoV-2 new variants GRP78 infectivity Biology (General) QH301-705.5 Abbas Khan Anwar Mohammad Inamul Haq Mohammad Nasar Waqar Ahmad Qudsia Yousafi Muhammad Suleman Sajjad Ahmad Aqel Albutti Taimoor Khan Sulaiman K. Marafie Eman Alshawaf Syed Shujait Ali Jehad Abubaker Dong-Qing Wei Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity
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	article
author	Abbas Khan Anwar Mohammad Inamul Haq Mohammad Nasar Waqar Ahmad Qudsia Yousafi Muhammad Suleman Sajjad Ahmad Aqel Albutti Taimoor Khan Sulaiman K. Marafie Eman Alshawaf Syed Shujait Ali Jehad Abubaker Dong-Qing Wei
author_facet	Abbas Khan Anwar Mohammad Inamul Haq Mohammad Nasar Waqar Ahmad Qudsia Yousafi Muhammad Suleman Sajjad Ahmad Aqel Albutti Taimoor Khan Sulaiman K. Marafie Eman Alshawaf Syed Shujait Ali Jehad Abubaker Dong-Qing Wei
author_sort	Abbas Khan
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_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_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_sort	structural-dynamics and binding analysis of rbd from sars-cov-2 variants of concern (vocs) and grp78 receptor revealed basis for higher infectivity
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/eca055d1a3644e9792cfcca8455fd873
work_keys_str_mv	AT abbaskhan structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT anwarmohammad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT inamulhaq structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT mohammadnasar structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT waqarahmad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT qudsiayousafi structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT muhammadsuleman structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT sajjadahmad structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT aqelalbutti structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT taimoorkhan structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT sulaimankmarafie structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT emanalshawaf structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT syedshujaitali structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT jehadabubaker structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity AT dongqingwei structuraldynamicsandbindinganalysisofrbdfromsarscov2variantsofconcernvocsandgrp78receptorrevealedbasisforhigherinfectivity
_version_	1718411233017724928

Structural-Dynamics and Binding Analysis of RBD from SARS-CoV-2 Variants of Concern (VOCs) and GRP78 Receptor Revealed Basis for Higher Infectivity

Ejemplares similares