Poster Presentation 12th Australasian Virology Society Meeting 2024

In Silico Comparison of Omicron SARS-CoV 2 Spike Protein Binding Affinity with Rodent ACE2 Predicts that a Broad Range of Rodents are Susceptible to SARS-CoV 2 Infection (#226)

Timothy Penn 1 , Jillian Carr 1
  1. Flinders University, ., SA, Australia

The potential for spillover of SARS-CoV 2 from humans to animals has been investigated since the beginning of the COVID-19 pandemic.  Due to their large populations and close proximity to humans, rodents represent an important potential reservoir for SARS-CoV 2 should they be susceptible to infection.  A key determinant of species risk to SARS-CoV 2 infection is the ability for the SARS-CoV 2 Spike protein to bind to the host's ACE2.  Initial studies investigating the interactions of ancestral SARS-CoV 2 Spike protein with the ACE2 of various animals indicated that most rodents, notably Mus musculuswere not at risk from SARS-CoV 2 infection.  However, it has since been discovered that the SARS-CoV 2 Omicron variant contains mutations within its Spike protein that allows it to infect Mus musculuswhich suggests that other rodents non-permissible to ancestral SARS-CoV 2 may now be at risk from the Omicron variant.  To investigate this risk, we compared the ACE2 sequences of 58 rodent species within the context of the interactions seen between Omicron Spike and mouse ACE2.  We also calculated the difference in binding energy within a mouse ACE2/Omicron Spike complex caused by ACE2 residue variations seen in each of these rodent species.  Our data indicate that the Omicron Spike protein has a high binding affinity for the ACE2 of most, if not all, of the investigated rodents, suggesting that a wide range of rodents are now at risk from SARS-CoV 2 infection.  This emphasizes the need for the control of rodent populations and the surveillance of SARS-CoV 2 within susceptible rodents.

  1. Lam, S.D., Bordin, N., Waman, V.P. et al. SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals. Sci Rep 10, 16471 (2020). https://doi.org/10.1038/s41598-020-71936-5
  2. Zhang W, Shi K, Geng Q, Ye G, Aihara H, Li F. Structural basis for mouse receptor recognition by SARS-CoV-2 omicron variant. Proc Natl Acad Sci U S A. 2022 Nov;119(44):e2206509119. doi: 10.1073/pnas.2206509119. Epub 2022 Oct 18. PMID: 36256797; PMCID: PMC9636943.