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Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) recep...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Cold Spring Harbor Laboratory
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328061/ https://www.ncbi.nlm.nih.gov/pubmed/34341794 http://dx.doi.org/10.1101/2021.07.23.453598 |
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author | Kim, Seonghan Liu, Yi Lei, Zewei Dicker, Jeffrey Cao, Yiwei Zhang, X. Frank Im, Wonpil |
author_facet | Kim, Seonghan Liu, Yi Lei, Zewei Dicker, Jeffrey Cao, Yiwei Zhang, X. Frank Im, Wonpil |
author_sort | Kim, Seonghan |
collection | PubMed |
description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as the variants of concern according to the US CDC. In this study, we performed both all-atom steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to characterize the binding interactions between ACE2 and RBD of all current variants of concern (Alpha, Beta, Gamma, and Delta) and two variants of interest (Epsilon and Kappa). We report that the RBD of the Alpha (N501Y) variant requires the highest amount of force initially to be detached from ACE2 due to the N501Y mutation in addition to the role of N90-glycan, followed by Beta/Gamma (K417N/T, E484K, and N501Y) or Delta (L452R and T478K) variant. Among all variants investigated in this work, the RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2. Our results combined SMD simulations and MST experiments indicate what makes each variant more contagious in terms of RBD and ACE2 interactions. This study could help develop new drugs to inhibit SARS-CoV-2 entry effectively. |
format | Online Article Text |
id | pubmed-8328061 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-83280612021-08-03 Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern Kim, Seonghan Liu, Yi Lei, Zewei Dicker, Jeffrey Cao, Yiwei Zhang, X. Frank Im, Wonpil bioRxiv Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as the variants of concern according to the US CDC. In this study, we performed both all-atom steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to characterize the binding interactions between ACE2 and RBD of all current variants of concern (Alpha, Beta, Gamma, and Delta) and two variants of interest (Epsilon and Kappa). We report that the RBD of the Alpha (N501Y) variant requires the highest amount of force initially to be detached from ACE2 due to the N501Y mutation in addition to the role of N90-glycan, followed by Beta/Gamma (K417N/T, E484K, and N501Y) or Delta (L452R and T478K) variant. Among all variants investigated in this work, the RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2. Our results combined SMD simulations and MST experiments indicate what makes each variant more contagious in terms of RBD and ACE2 interactions. This study could help develop new drugs to inhibit SARS-CoV-2 entry effectively. Cold Spring Harbor Laboratory 2021-07-26 /pmc/articles/PMC8328061/ /pubmed/34341794 http://dx.doi.org/10.1101/2021.07.23.453598 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Kim, Seonghan Liu, Yi Lei, Zewei Dicker, Jeffrey Cao, Yiwei Zhang, X. Frank Im, Wonpil Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title | Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title_full | Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title_fullStr | Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title_full_unstemmed | Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title_short | Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern |
title_sort | differential interactions between human ace2 and spike rbd of sars-cov-2 variants of concern |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328061/ https://www.ncbi.nlm.nih.gov/pubmed/34341794 http://dx.doi.org/10.1101/2021.07.23.453598 |
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