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The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective

Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at th...

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Autores principales: Khan, Abbas, Gui, Jianjun, Ahmad, Waqar, Haq, Inamul, Shahid, Marukh, Khan, Awais Ahmed, Shah, Abdullah, Khan, Arsala, Ali, Liaqat, Anwar, Zeeshan, Safdar, Muhammad, Abubaker, Jehad, Uddin, N. Nizam, Cao, Liqiang, Wei, Dong-Qing, Mohammad, Anwar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040812/
https://www.ncbi.nlm.nih.gov/pubmed/35480256
http://dx.doi.org/10.1039/d1ra04694b
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author Khan, Abbas
Gui, Jianjun
Ahmad, Waqar
Haq, Inamul
Shahid, Marukh
Khan, Awais Ahmed
Shah, Abdullah
Khan, Arsala
Ali, Liaqat
Anwar, Zeeshan
Safdar, Muhammad
Abubaker, Jehad
Uddin, N. Nizam
Cao, Liqiang
Wei, Dong-Qing
Mohammad, Anwar
author_facet Khan, Abbas
Gui, Jianjun
Ahmad, Waqar
Haq, Inamul
Shahid, Marukh
Khan, Awais Ahmed
Shah, Abdullah
Khan, Arsala
Ali, Liaqat
Anwar, Zeeshan
Safdar, Muhammad
Abubaker, Jehad
Uddin, N. Nizam
Cao, Liqiang
Wei, Dong-Qing
Mohammad, Anwar
author_sort Khan, Abbas
collection PubMed
description Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618.
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spelling pubmed-90408122022-04-26 The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective Khan, Abbas Gui, Jianjun Ahmad, Waqar Haq, Inamul Shahid, Marukh Khan, Awais Ahmed Shah, Abdullah Khan, Arsala Ali, Liaqat Anwar, Zeeshan Safdar, Muhammad Abubaker, Jehad Uddin, N. Nizam Cao, Liqiang Wei, Dong-Qing Mohammad, Anwar RSC Adv Chemistry Continuing reports of new SARS-CoV-2 variants have caused worldwide concern and created a challenging situation for clinicians. The recently reported variant B.1.618, which possesses the E484K mutation specific to the receptor-binding domain (RBD), as well as two deletions of Tyr145 and His146 at the N-terminal binding domain (NTD) of the spike protein, must be studied in depth to devise new therapeutic options. Structural variants reported in the RBD and NTD may play essential roles in the increased pathogenicity of this SARS-CoV-2 new variant. We explored the binding differences and structural-dynamic features of the B.1.618 variant using structural and biomolecular simulation approaches. Our results revealed that the E484K mutation in the RBD slightly altered the binding affinity through affecting the hydrogen bonding network. We also observed that the flexibility of three important loops in the RBD required for binding was increased, which may improve the conformational optimization and consequently binding of the new variant. Furthermore, we found that deletions of Tyr145 and His146 at the NTD reduced the binding affinity of the monoclonal antibody (mAb) 4A8, and that the hydrogen bonding network was significantly affected consequently. This data show that the new B.1.618 variant is an antibody-escaping variant with slightly altered ACE2–RBD affinity. Moreover, we provide insights into the binding and structural-dynamics changes resulting from novel mutations in the RBD and NTD. Our results suggest the need for further in vitro and in vivo studies that will facilitate the development of possible therapies for new variants such as B.1.618. The Royal Society of Chemistry 2021-09-09 /pmc/articles/PMC9040812/ /pubmed/35480256 http://dx.doi.org/10.1039/d1ra04694b Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by-nc/3.0/
spellingShingle Chemistry
Khan, Abbas
Gui, Jianjun
Ahmad, Waqar
Haq, Inamul
Shahid, Marukh
Khan, Awais Ahmed
Shah, Abdullah
Khan, Arsala
Ali, Liaqat
Anwar, Zeeshan
Safdar, Muhammad
Abubaker, Jehad
Uddin, N. Nizam
Cao, Liqiang
Wei, Dong-Qing
Mohammad, Anwar
The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title_full The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title_fullStr The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title_full_unstemmed The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title_short The SARS-CoV-2 B.1.618 variant slightly alters the spike RBD–ACE2 binding affinity and is an antibody escaping variant: a computational structural perspective
title_sort sars-cov-2 b.1.618 variant slightly alters the spike rbd–ace2 binding affinity and is an antibody escaping variant: a computational structural perspective
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040812/
https://www.ncbi.nlm.nih.gov/pubmed/35480256
http://dx.doi.org/10.1039/d1ra04694b
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