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

Cheng, R. R.; Dodero-Rojas, E.; Di Pierro, M.; Onuchic, J. N.

2021-03-26 biophysics
10.1101/2021.03.25.437113 bioRxiv
Show 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.

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