ArticleProceedings of the National Academy of Sciences of the United States of America2020
Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 436 papers.
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436 citing papers in PubMed, 681 citations in OpenAlex.
- Rethinking non-human primate models for emerging viral infections after COVID-19.Laboratory animal research · 2026Review
- Broad-spectrum CRISPR-Cas13d-mediated strategy for combating human coronaviruses.Molecular therapy. Nucleic acids · 2026Article
- Human angiotensin‑converting enzyme 2‑specific benzothiazole-based allosteric inhibitor against pan‑sarbecoviruses.Nature communications · 2026Article
- Species- and variant-specific ACE2 compatibility shapes SARS-CoV-2 spillover potential in North American cervids.Nature communications · 2026Article
- Serological Survey of SARS-CoV-2 in Wild Canids in Serbia: First Report in Red Foxes and Golden Jackals.Veterinary sciences · 2026Article
- Systematic multi-reference vertebrate ACE2 sequence similarity analysis predicts species susceptibility to SARS-related sarbecoviruses.Scientific reports · 2026Article
- Structural Constraints Acting on the SARS-CoV-2 Spike Protein Reveal Limited Space for Viral Adaptation.Genome biology and evolution · 2026Article
- Viral receptors as host-pathogen control nodes linking entry, signalling, and system-level pathogenesis.FEMS microbiology reviews · 2026Review
- Glucocorticoids suppress early lung inflammation and impair control of SARS-CoV-2 in non-human primates.PloS one · 2026Article
- Experimental evolution of Rc-o319 sarbecovirus spike protein reveals limited ACE2 adaptability.Virus evolution · 2026Article
- SARS-CoV-2 at the human-pet interface: transmission and pre-existing immunity in pets within infected households.Frontiers in veterinary science · 2026Article
- Natural Fatty Acids as Dual ACE2-Inflammatory Modulators: Integrated Computational Framework for Pandemic Preparedness.International journal of molecular sciences · 2025Article
- Screening for SARS-CoV-2 in different sheep and goat breeds in Türkiye using in-house ELISAs and real-time PCR.Tropical animal health and production · 2025Article
- Molecular insights into species-specific ACE2 recognition of coronavirus HKU5.Nature communications · 2025Article
- Novel ACE2 binding in bat merbecoviruses expands potential host range.PLoS pathogens · 2025Article
- Article
- SARS-CoV-2 Evolution in Humans Enables Its Transmission to Nonhuman Primates.Molecular biology and evolution · 2025Article
- Dynamic Allostery: Evolution's Double-Edged Sword in Protein Function and Disease.Journal of molecular biology · 2025Review
- Article
- Permissiveness of American bison to infection with severe acute respiratory syndrome coronavirus-2.Scientific reports · 2025Article
376 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 11 institutions in 5 countries.
Funding
Abstract
The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of COVID-19. The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of ACE2 sequences from 410 vertebrate species, including 252 mammals, to study the conservation of ACE2 and its potential to be used as a receptor by SARS-CoV-2. We designed a five-category binding score based on the conservation properties of 25 amino acids important for the binding between ACE2 and the SARS-CoV-2 spike protein. Only mammals fell into the medium to very high categories and only catarrhine primates into the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 spike protein binding and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (frequency <0.001) variants in 10/25 binding sites. In addition, we found significant signals of selection and accelerated evolution in the ACE2 coding sequence across all mammals, and specific to the bat lineage. Our results, if confirmed by additional experimental data, may lead to the identification of intermediate host species for SARS-CoV-2, guide the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.
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