The novel coronavirus (SARS-CoV-2), responsible for over 40 million infections and one million deaths globally, has posed a significant public health challenge. As this virus infects both humans and animals, understanding the interactions between SARS-CoV-2 and its potential animal hosts is crucial for both public and veterinary health. With the discovery of angiotensin-converting enzyme 2 (ACE2) as the virus functional receptor, efforts to develop antiviral treatments and vaccines have advanced. However, the resistance of mice to SARS-CoV-2 has intensified the search for alternative animal models. In this study phylogenetic analysis was conducted by utilizing MEGA X (v10.1.7) with the JTT substitution model and 100 bootstrap replicates. Protein sequence alignment was performed via ClustalW2. The distribution of ACE2 expression was analyzed utilizing the GTEx portal, GEO database, and the ggplot2 software for statistical analysis. ACE2 expression across several organs was assessed using the Human Protein Atlas, whereas protein-protein interactions were investigated through the STRING database. This study analyzes ACE2 evolutionary history and expression across mammalian species, identifying the crab-eating macaque as a strong candidate due to its five identical ACE2 hotspot residues with humans. Other species, including cattle, pigs, ferrets, and cats, share varying degrees of similarity. ACE2 expression patterns, particularly in lung and colon tissues, are also highlighted across species. These findings offer valuable insights for selecting optimal animal models to accelerate COVID-19 research and therapeutic development.

To Cite This Article: Ali A, Irshad U, Ji Z, Azmat U, Akbar K, Xin T, Su Z, 2025. ACE2 Expression Patterns Across Mammals and Key Findings for SARS-CoV-2 Model Development for Human and Animal Research. Pak Vet J, 45(1): 312-319. http://dx.doi.org/10.29261/pakvetj/2025.142