SARS-CoV-2 spike protein predicted to form stable complexes with host receptor protein orthologues from mammals, but not fish, birds or reptiles

The coronavirus disease 2019 (COVID-19) global pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein binds to its receptor, angiotensin-converting enzyme 2 (ACE2), and is then processed by transmembrane protease serine 2 (TMPRSS2). Whilst receptor binding contributes to the viral host range, changes in energy of spike protein:ACE2 complexes in other animals have not been widely explored. Here, we analyse interactions between the spike protein and orthologues of ACE2 and TMPRSS2 from a broad range of 215 vertebrate species. Using models of spike protein:ACE2 orthologue complexes, we calculated their changes in energy, correlated to mammalian COVID-19 infection data. Across vertebrates, mutations are predicted to have more impact on the function of ACE2 than TMPRSS2. Finally, we provide phylogenetic analysis demonstrating that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but not fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.