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Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron
The Omicron variant of SARS-CoV-2 emerged in South African in late 2021. This variant has a large number of mutations, and regarded as fastest-spreading Covid variant. The spike RBD region of SARS-CoV-2 and its interaction with human ACE2 play fundamental role in viral infection and transmission. To...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier B.V.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339243/ https://www.ncbi.nlm.nih.gov/pubmed/35937157 http://dx.doi.org/10.1016/j.molstruc.2022.133842 |
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author | Shirzadeh, Maryam Monhemi, Hassan Eftekhari, Mohammad |
author_facet | Shirzadeh, Maryam Monhemi, Hassan Eftekhari, Mohammad |
author_sort | Shirzadeh, Maryam |
collection | PubMed |
description | The Omicron variant of SARS-CoV-2 emerged in South African in late 2021. This variant has a large number of mutations, and regarded as fastest-spreading Covid variant. The spike RBD region of SARS-CoV-2 and its interaction with human ACE2 play fundamental role in viral infection and transmission. To explore the reason of fast-spreading properties of Omicron variant, we have modeled the interactions of Omicron RBD and human ACE2 using docking and molecular dynamics simulations. Results show that RBD-ACE2 binding site may drastically relocate with an enlarged interface. The predicted interface has large negative binding energies and shows stable conformation in molecular dynamics simulations. It was found that the interfacial area in Omicron RBD-ACE2 complex is increased up to 40% in comparison to wild-type Sars-Cov-2. Moreover, the number of hydrogen bonds significantly increased up to 80%. The key interacting residues become also very different in Omicron variant. The new binding interface can significantly accommodate R403, as a key RBD residue, near ACE2 surface which leads to two new strong salt bridges. The exploration of the new binding interface can help to understand the reasons of high transmission rate of Omicron. |
format | Online Article Text |
id | pubmed-9339243 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93392432022-08-01 Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron Shirzadeh, Maryam Monhemi, Hassan Eftekhari, Mohammad J Mol Struct Article The Omicron variant of SARS-CoV-2 emerged in South African in late 2021. This variant has a large number of mutations, and regarded as fastest-spreading Covid variant. The spike RBD region of SARS-CoV-2 and its interaction with human ACE2 play fundamental role in viral infection and transmission. To explore the reason of fast-spreading properties of Omicron variant, we have modeled the interactions of Omicron RBD and human ACE2 using docking and molecular dynamics simulations. Results show that RBD-ACE2 binding site may drastically relocate with an enlarged interface. The predicted interface has large negative binding energies and shows stable conformation in molecular dynamics simulations. It was found that the interfacial area in Omicron RBD-ACE2 complex is increased up to 40% in comparison to wild-type Sars-Cov-2. Moreover, the number of hydrogen bonds significantly increased up to 80%. The key interacting residues become also very different in Omicron variant. The new binding interface can significantly accommodate R403, as a key RBD residue, near ACE2 surface which leads to two new strong salt bridges. The exploration of the new binding interface can help to understand the reasons of high transmission rate of Omicron. Elsevier B.V. 2022-12-15 2022-07-31 /pmc/articles/PMC9339243/ /pubmed/35937157 http://dx.doi.org/10.1016/j.molstruc.2022.133842 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Article Shirzadeh, Maryam Monhemi, Hassan Eftekhari, Mohammad Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title | Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title_full | Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title_fullStr | Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title_full_unstemmed | Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title_short | Large interfacial relocation in RBD-ACE2 complex may explain fast-spreading property of Omicron |
title_sort | large interfacial relocation in rbd-ace2 complex may explain fast-spreading property of omicron |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339243/ https://www.ncbi.nlm.nih.gov/pubmed/35937157 http://dx.doi.org/10.1016/j.molstruc.2022.133842 |
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