SARS-CoV-2 can transmit efficiently in humans, but it is less clear which other mammals are at risk of being infected. SARS-CoV-2 encodes a Spike (S) protein that binds to human ACE2 receptor to mediate cell entry. A species with a human-like ACE2 receptor could therefore be at risk of being infected by SARS-CoV-2. We compared between 132 mammalian ACE2 genes and between 17 coronavirus S proteins. We showed that while global similarities reflected by whole ACE2 gene alignments are poor predictors of high-risk mammals, local similarities at key S protein-binding sites highlight several high-risk mammals that share good ACE2 homology with human. Bats are likely reservoirs of SARS-CoV-2, but there are other high-risk mammals that share better ACE2 homologies with human. Both SARS-CoV-2 and SARS-CoV are closely related to bat coronavirus. Yet, among host-specific coronaviruses infecting high-risk mammals, key ACE2-binding sites on S proteins share highest similarities between SARS-CoV-2 and Pangolin-CoV and between SARS-CoV and Civet-CoV. These results suggest that direct coronavirus transmission from bat to human is unlikely, and that rapid adaptation of a bat SARS-like coronavirus in different high-risk intermediate hosts could have allowed it to acquire distinct high binding potential between S protein and human-like ACE2 receptors.
【저자키워드】 Evolution, Molecular biology, genetics, 【초록키워드】 SARS-CoV-2, ACE2, coronavirus, S protein, spike, SARS-CoV, ACE2 receptor, risk, Local, Transmission, Protein, humans, ACE2 receptors, bat, predictor, binding, similarity, ACE2 gene, cell entry, S proteins, homology, human ACE2 receptor, mammals, reservoir, ENCODE, mammalian, SARS-like coronavirus, infecting, Host, highlight, bind, highest, unlikely, reflected, less, mammal, ACE2-binding site, 【제목키워드】 SARS-CoV-2, ACE2, risk, Perspective, mammalian,