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Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility

View ORCID ProfileRyan R. Cheng, View ORCID ProfileEsteban Dodero-Rojas, Michele Di Pierro, View ORCID ProfileJosé N. Onuchic
doi: https://doi.org/10.1101/2021.03.25.437113
Ryan R. Cheng
1Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005
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  • For correspondence: ryan.r.cheng@gmail.com jonuchic@rice.edu
Esteban Dodero-Rojas
1Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005
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Michele Di Pierro
1Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005
2Department of Physics, Northeastern University, Boston, Massachusetts 02115
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José N. Onuchic
1Center for Theoretical Biological Physics, Rice University, Houston, Texas 77005
3Department of Chemistry, Rice University, Houston, Texas 77005
4Department of Physics & Astronomy, Rice University, Houston, Texas 77005
5Department of Biosciences, Rice University, Houston, Texas 77005
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  • For correspondence: ryan.r.cheng@gmail.com jonuchic@rice.edu
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Abstract

We explore the energetic frustration patterns associated with the binding between the SARS-CoV-2 spike protein and the ACE2 receptor protein in a broad selection of animals. Using energy landscape theory and the concept of energy frustration—theoretical tools originally developed to study protein folding—we are able to identify interactions among residues of the spike protein and ACE2 that result in COVID-19 resistance. This allows us to identify whether or not a particular animal is susceptible to COVID-19 from the protein sequence of ACE2 alone. Our analysis predicts a number of experimental observations regarding COVID-19 susceptibility, demonstrating that this feature can be explained, at least partially, on the basis of theoretical means.

Competing Interest Statement

The authors have declared no competing interest.

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Posted April 07, 2021.
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Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility
Ryan R. Cheng, Esteban Dodero-Rojas, Michele Di Pierro, José N. Onuchic
bioRxiv 2021.03.25.437113; doi: https://doi.org/10.1101/2021.03.25.437113
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Evolutionary differences in the ACE2 reveals the molecular origins of COVID-19 susceptibility
Ryan R. Cheng, Esteban Dodero-Rojas, Michele Di Pierro, José N. Onuchic
bioRxiv 2021.03.25.437113; doi: https://doi.org/10.1101/2021.03.25.437113

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