tetano
Editor, Senior Moderator
PLoS Comput Biol
. 2020 Dec 3;16(12):e1008449.
doi: 10.1371/journal.pcbi.1008449. eCollection 2020 Dec.
Insights on cross-species transmission of SARS-CoV-2 from structural modeling
Jo?o P G L M Rodrigues[SUP] 1 [/SUP], Susana Barrera-Vilarmau[SUP] 2 [/SUP], Jo?o M C Teixeira[SUP] 3 [/SUP], Marija Sorokina[SUP] 4 [/SUP], Elizabeth Seckel[SUP] 5 [/SUP], Panagiotis L Kastritis[SUP] 4 [/SUP], Michael Levitt[SUP] 1 [/SUP]
Affiliations
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 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 and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. 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 allow us to 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.
. 2020 Dec 3;16(12):e1008449.
doi: 10.1371/journal.pcbi.1008449. eCollection 2020 Dec.
Insights on cross-species transmission of SARS-CoV-2 from structural modeling
Jo?o P G L M Rodrigues[SUP] 1 [/SUP], Susana Barrera-Vilarmau[SUP] 2 [/SUP], Jo?o M C Teixeira[SUP] 3 [/SUP], Marija Sorokina[SUP] 4 [/SUP], Elizabeth Seckel[SUP] 5 [/SUP], Panagiotis L Kastritis[SUP] 4 [/SUP], Michael Levitt[SUP] 1 [/SUP]
Affiliations
- PMID: 33270653
- DOI: 10.1371/journal.pcbi.1008449
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 31 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 and confirmed cases of cross-species transmission, the question of the extent to which this transmission is possible emerges, as well as what molecular features distinguish susceptible from non-susceptible animal species. 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 allow us to 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.