Comparative analyses of ACE2 and TMPRSS2 gene: Implications for the risk to which vertebrate animals are susceptible to SARS‐CoV‐2

Huang, Chen; Jiang, Yu; Yan, Jie

Along with the control and prevention of coronavirus disease 2019 transmission, infected animals might have potential to carry the virus to spark new outbreaks. However, very few studies explore the susceptibility of animals to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Viral attachment as a crucial step for cross‐species infection requires angiotensin‐converting enzyme 2 (ACE2) as a receptor and depends on TMPRSS2 protease activity. Here, we searched the genomes of metazoans from different classes using an extensive BLASTP survey and found ACE2 and TMPRSS2 occur in vertebrates, but some vertebrates lack Tmprss2. We identified 6 amino acids among 25 known human ACE2 residues are highly associated with the binding of ACE2 to SARS‐CoV‐2 (p value < .01) by Fisher exact test, and following this, calculated the probability of viral attachment within each species by the randomForest function from R randomForest library. Furthermore, we observed that Ace2 selected from seven animals based on the above analysis lack the hydrophobic contacts identified on human ACE2, indicating less affinity of SARS‐CoV‐2 to Ace2 in animals than humans. Finally, the alignment of 3D structure between human ACE2 and other animals by I‐TASSER and TM‐align displayed a reasonable structure for viral attachment within these species. Taken together, our data may shed light on the human‐to‐animal transmission of SARS‐CoV‐2.