Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Exhibits High Predicted Binding Affinity to ACE2 from Lagomorphs (Rabbits and Pikas)

SIMPLE SUMMARY: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic COVID-19. The virus infects human cells by binding of the virus spike to the cell receptor ACE2. Some studies suggest that dogs, cats and other animal species could be infected by SARS-CoV-2, while very limited data are available on lagomorphs. There are several occasions where rabbits and other lagomorphs are in close contact with humans. To investigate the interaction between SARS-CoV-2 spikes and ACE2 of lagomorphs, predictive computer-based models were used in this study. The structure of ACE2 of lagomorphs was obtained on the basis of the amino acid sequences computationally. The interaction with the model of SARS-CoV-2 spikes was studied and described in depth on the basis of the complex human ACE2-SARS-CoV-2 published before. The interaction among SARS-CoV-2 spikes and ACE2 of other companion or laboratory animals is also described for comparative purposes. The results predict that ACE2 of lagomorphs are likely to bind SARS-CoV-2 spikes and suggest that further studies would be justified to confirm these results and to evaluate the risks to humans being in close contact with lagomorphs, such as veterinarians, farmers, slaughterhouse workers, butchers or pet owners. ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic COVID-19. The virus infects human cells by binding of the virus spike to the cell receptor ACE2. The crystal structure of SARS-CoV-2 spikes in complex with human ACE2 has recently been solved, and the main amino acid residues involved in the virus–receptor complex have been detected. To investigate the affinity of ACE2 of lagomorphs to the SARS-CoV-2 spike, ACE2 sequences from rabbits and American pikas were compared with human ACE2 and with ACE2 from mammals with different susceptibility to the virus. Models of the complex formed by SARS-CoV-2 spike and ACE2 from lagomorphs and from other mammals were created for comparative studies. ACE2 of lagomorphs showed fewer substitutions than human ACE2 in residues involved in the ACE2-SARS-CoV-2 spike complex, similar to cats. Analysis of the binding interface of the simulated complexes ACE2-SARS-CoV-2 spike showed high affinity of the ACE2 of lagomorphs to the viral spike protein. These findings suggest that the spike of SARS-CoV-2 could bind the ACE2 receptor of lagomorphs, and future studies should investigate the role of lagomorphs in SARS-CoV-2 epidemiology. Furthermore, the risks to humans coming into close contacts with these animals should be evaluated.