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Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern

View ORCID ProfileSeonghan Kim, Yi Liu, Zewei Lei, Jeffrey Dicker, View ORCID ProfileYiwei Cao, View ORCID ProfileX. Frank Zhang, View ORCID ProfileWonpil Im
doi: https://doi.org/10.1101/2021.07.23.453598
Seonghan Kim
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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Yi Liu
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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Zewei Lei
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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Jeffrey Dicker
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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Yiwei Cao
2Departments of Biological Sciences, Chemistry, and Computer Science and Engineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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X. Frank Zhang
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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  • For correspondence: xiz310@lehigh.edu wonpil@lehigh.edu
Wonpil Im
1Department of Bioengineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
2Departments of Biological Sciences, Chemistry, and Computer Science and Engineering, Lehigh University, 111 Research Dr, Bethlehem, PA 18015, USA
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  • For correspondence: xiz310@lehigh.edu wonpil@lehigh.edu
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ABSTRACT

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.

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Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 26, 2021.
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Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern
Seonghan Kim, Yi Liu, Zewei Lei, Jeffrey Dicker, Yiwei Cao, X. Frank Zhang, Wonpil Im
bioRxiv 2021.07.23.453598; doi: https://doi.org/10.1101/2021.07.23.453598
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Differential Interactions Between Human ACE2 and Spike RBD of SARS-CoV-2 Variants of Concern
Seonghan Kim, Yi Liu, Zewei Lei, Jeffrey Dicker, Yiwei Cao, X. Frank Zhang, Wonpil Im
bioRxiv 2021.07.23.453598; doi: https://doi.org/10.1101/2021.07.23.453598

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