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Insights on cross-species transmission of SARS-CoV-2 from structural modeling

By Joao P.G.L.M. Rodrigues, Susana Barrera-Vilarmau, João MC Teixeira, Elizabeth Seckel, Panagiotis Kastritis, Michael Levitt

Posted 05 Jun 2020
bioRxiv DOI: 10.1101/2020.06.05.136861 (published DOI: 10.1371/journal.pcbi.1008449)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 14 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results. ### Competing Interest Statement The authors have declared no competing interest.

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