Interacting Proteins, Polymorphisms and the Susceptibility of Animals to SARS-CoV-2

Simple Summary COVID-19 is the disease caused by a coronavirus: SARS-CoV-2. The disease was declared by WHO in March 2020 as a pandemic and is still affecting countries around the world. Although considered a human disease, it is thought to have its origins in bats, and transmitted to humans potentially through an intermediate animal. What is not fully understood is the likelihood of the virus transmitting back to animal populations, either to companion or wild animals. For the virus to enter host cells, it needs to interact with particular proteins on the cell surface. Here we review the susceptibility of animals to the SARS-CoV-2 virus through the comparison of proteins between animals and humans. The most studied is the angiotensin-converting enzyme 2 receptor (ACE2), which has been used to rank the viral susceptibility of a range of vertebrates. Here, we also assess three other proteins. Of these, TMPRSS2 may be helpful in determining susceptibility, whereas the other two would appear to be of limited use. We propose that future work should examine changes seen in these proteins which alter the ease by which the virus can enter cells. This type of analysis may contribute limited evidence in predicting if animals are safe from such viruses and may help to guide future welfare concerns. COVID-19, caused by SARS-CoV-2, is a world-wide problem for the human population. It is known that some animal species, such as mink, can become infected and transmit the virus. However, the susceptibility of most animals is not known. Here, we review the use of sequence analysis of the proteins which are known to interact with SARS-CoV-2 as a way to estimate an animal's susceptibility. Although most such work concentrates on the angiotensin-converting enzyme 2 receptor (ACE2), here TMPRSS2 (Transmembrane Serine Protease 2), neuropilin-1 and furin are also considered. Polymorphisms, especially ones which are known to alter viral/host interactions are also discussed. Analysis of ACE2 and TMPRSS2 protein sequences across species suggests this approach may be of some utility in predicting susceptibility; however, this analysis fails to highlight some susceptible animals such as mink. However, combined with observational data which emerges over time about which animals actually become infected, this may, in the future, be a useful tool to assist the management of risks associated with human/animal contact and support conservation and animal welfare measures.