COVID-19: Why Some Animals Are More Susceptible Than Others

3D modeling of the protein receptors that allow SARS-CoV-2 to enter various animal cells has revealed unique structural features that are necessary for infection. This knowledge could help guide the development of new drugs and predict future outbreaks.   Some animals are more susceptible to SARS-CoV-2 infection than others. While humans appear to be the primary target of the coronavirus, cats and cattle, for example, also seem to be susceptible to infection. Conversely, pigs and chickens do not appear to be affected. But how can we explain such a difference? This is the question that researchers at Stanford University in California have sought to answer. They sought to understand why some animals appear to be immune to SARS-CoV-2 while others are not. In a new 3D modeling study, the scientists point to the distinct structural characteristics of a protein found on the surface of animal cells. To reach this conclusion, Rodrigues and his colleagues looked for clues during the first stage of infection, when the virus comes into contact with and recognizes the cells it can infect. At that point, the SARS-CoV-2 spike protein binds to the ACE2 receptor on the surface of animal cells. By modeling and simulating the 3D structures of these proteins, the researchers were able to study their interactions. The process was repeated for different animal species to determine their varying affinities—a process that is ultimately akin to trying to understand which locks are activated by a particular key, in this case the SARS-CoV-2 protein. It then became clear that certain ACE2 “locks” in animals are more compatible than others and interact better with the viral “key.” Humans are, of course, included in this group, but they are not the only ones. 3D modeling has made it possible to identify structural characteristics unique to the ACE2 receptors of these susceptible species. Without these characteristics, the animals appear to be immune to COVID-19. Their ACE2 protein does not interact well enough with the viral protein to allow infection by the virus. These findings could facilitate the development of antiviral strategies. For example, researchers are considering using artificial “locks” to trap SARS-CoV-2 and prevent it from interacting with human receptors. But this research could also have a broader impact by improving surveillance models for potential animal reservoirs from which the virus could jump to humans, ultimately helping to prevent future outbreaks.