Lions, Tigers and Kittens too: ACE2 and susceptibility to CoVID-19

Mathavarajah, Sabateeshan; Dellaire, Graham

SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has been reported to infect domesticated animals in a species-specific manner, where cats were susceptible but not dogs. Using the recently published crystal structure of the SARS-CoV-2 spike protein complexed with the human host cell receptor ACE2, we characterized the structure and evolution of ACE2 in several of these species and identify a single interacting amino acid residue conserved between human and Felidae ACE2 but not in Canidae that correlates with virus susceptibility. Using computational analyses we describe how this site likely affects ACE2 targeting by the virus. Thus, we highlight how evolution-based approaches can be used to form hypotheses and study animal transmission of such viruses in the future. Lay summary: Recently, the virus that causes COVID-19 was shown to transmit to companion animals. A single genetic change in the host receptor for the virus inherited in cats, but not dogs, correlates with feline susceptibility. With human-to-cat transmission of COVID-19 confirmed, such information can inform public health policy regarding companion animals.