Bioinformatic evaluation of the potential animal models for studying SARS-Cov-2

Area of Science:

• Virology
• Comparative Genomics
• Animal Modeling

Background:

• The COVID-19 pandemic, caused by SARS-CoV-2, has led to significant global health challenges.
• Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2, crucial for viral entry.
• Existing mouse models exhibit natural resistance to SARS-CoV-2, necessitating alternative animal models.

Purpose of the Study:

• To analyze the phylogenetic and expression patterns of ACE2 across various mammalian species.
• To identify potential animal models that can effectively mimic human susceptibility to SARS-CoV-2.
• To guide the selection of appropriate animal models for COVID-19 research and therapeutic development.

Main Methods:

• Comparative analysis of ACE2 gene sequences to identify conserved residues interacting with the SARS-CoV-2 spike protein.
• Examination of ACE2 expression levels in various tissues across different mammalian species.
• Phylogenetic analysis of ACE2 to understand evolutionary relationships and functional similarities.

Main Results:

• Crab-eating macaques share 5 identical hotspot residues in ACE2 with humans, suggesting high binding potential for SARS-CoV-2 spike protein.
• Cattle and pigs exhibit 4 identical sites, while ferrets, cats, and dogs show 3.
• Bats and mice have only 2 shared amino acids with human ACE2, indicating lower susceptibility.
• High ACE2 expression was observed in crab-eating macaque liver, lung, thyroid, and colon.
• In dogs, ACE2 is highly expressed in the colon, with notable sex-based differential expression.

Conclusions:

• Crab-eating macaques represent a strong candidate for SARS-CoV-2 animal modeling due to ACE2 homology.
• Comparative ACE2 analysis provides valuable insights for selecting appropriate animal models for COVID-19 research.
• Understanding ACE2 expression patterns across species is critical for developing effective antiviral strategies and vaccines.