Analysis of RBD-ACE2 interactions in livestock species as a factor in the spread of SARS-CoV-2 among animals

The high mutation rate of SARS-CoV-2, which has led to the emergence of a number of virus variants, creates risks of transmission from humans to animal species and the emergence of new animal reservoirs of COVID-19. This study aimed to identify animal species among livestock susceptible to infection and develop an approach that would be possible to use for assessing the hazards caused by new SARS-CoV-2 variants for animals. Bioinformatic analysis was used to evaluate the ability of receptor-binding domains (RBDs) of different SARS-CoV-2 variants to interact with ACE2 receptors of livestock species. The results indicated that the stability of RBD-ACE2 complexes depends on both amino acid residues in the ACE2 sequences of animal species and on mutations in the RBDs of SARS-CoV-2 variants, with the residues in the interface of the RBD-ACE2 complex being the most important. All studied SARS-CoV-2 variants had high affinity for ferret and American mink receptors, while the affinity for horse, donkey, and bird species' receptors significantly increased in the highly mutated Omicron variant. Hazards that future SARS-CoV-2 variants may acquire specificity to new animal species remain high given the mutability of the virus. The continued use and expansion of the bioinformatic approach presented in this study may be relevant for monitoring transmission risks and preventing the emergence of new reservoirs of COVID-19 among animals.