During the SARS-CoV epidemic, where civets were identified as the intermediate reservoir of infection, a shifting pattern of increasing and decreasing ACE2 usage was observed in individual isolates of SARS-CoV taken from civets and humans (although they shared approximately 99% similarity to each other), providing evidence for adaptation to individual host receptors [13,20] with a particular focus on differential adaptation to human ACE2 residues K31 (T31 in civets) and K353. This evidence concerns the gene ACE2 and infection.