RT Journal Article
SR Electronic
T1 Diversity of ACE2 and its interaction with SARS-CoV-2 receptor binding domain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.10.25.354548
DO 10.1101/2020.10.25.354548
A1 Low-Gan, Jessie
A1 Huang, Ruiqi
A1 Warner, Gabrielle
A1 Kelley, Abigail
A1 McGregor, Duncan
A1 Smider, Vaughn
YR 2020
UL http://biorxiv.org/content/early/2020/11/04/2020.10.25.354548.abstract
AB COVID-19, the clinical syndrome caused by the SARS-CoV-2 virus, has rapidly spread globally causing tens of millions of infections and over a million deaths. The potential animal reservoirs for SARS-CoV-2 are currently unknown, however sequence analysis has provided plausible potential candidate species. SARS-CoV-2 binds to the angiotensin I converting enzyme 2 (ACE2) to enable its entry into host cells and establish infection. We analyzed the binding surface of ACE2 from several important animal species to begin to understand the parameters for the ACE2 recognition by the SARS-CoV-2 spike protein receptor binding domain (RBD). We employed Shannon entropy analysis to determine the variability of ACE2 across its sequence and particularly in its RBD interacting region, and assessed differences between various species’ ACE2 and human ACE2. As cattle are a known reservoir for coronaviruses with previous human zoonotic transfer, and has a relatively divergent ACE2 sequence, we compared the binding kinetics of bovine and human ACE2 to SARS-CoV-2 RBD. This revealed a nanomolar binding affinity for bovine ACE2 but an approximate ten-fold reduction of binding compared to human ACE2. Since cows have been experimentally infected by SARS-CoV-2, this lower affinity sets a threshold for sequences with lower homology to human ACE2 to be able to serve as a productive viral receptor for SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.