Skip to main content
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2020 Oct 9;40(1):79–85. doi: 10.1002/zoo.21576

Predicting susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals using ACE2 protein sequence homology

Ashutosh Kumar 1,2,, Sada N Pandey 1,3, Vikas Pareek 1,4, Ravi K Narayan 1,2, Muneeb A Faiq 1,5, Chiman Kumari 1,6
PMCID: PMC7675721  PMID: 33034084

Abstract

The article is presenting a bioinformatics based method predicting susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals. Recently, there were reports of cats and ferrets, dogs, minks, golden hamster, rhesus monkeys, tigers, and lions testing for SARS‐CoV‐2 RNA which indicated for the possible interspecies viral transmission. Our method successfully predicted the susceptibility of these animals for contracting SARS‐CoV‐2 infection. This method can be used as a screening tool for guiding viral RNA testing for domestic and wildlife animals at risk of getting COVID‐19. We provide a list of the animals at risk of developing COVID‐19 based on the susceptibility score.

Keywords: ACE2, COVID‐19, pets, SARS‐CoV‐2, susceptibility, wildlife


Predicting susceptibility for SARS‐CoV‐2 infection using NCBI protein blast tool.

graphic file with name ZOO-40-79-g001.jpg

Research Highlights

  • Zoonotic spillover of SARS‐CoV‐2 from humans have been reported recently

  • Homology to viral cell entry receptor ACE2 can predict susceptibility for contracting SARS‐CoV‐2

  • On the basis of a paired homology to complete protein sequence and viral binding hotspots on ACE2, we provide a list of susceptible animals

1. INTRODUCTION

The ongoing epidemic of COVID‐19 is a global concern for human health, but its impact on domestic and wildlife animals is largely unevaluated. The epidemic was believed to have started from the wet wildlife market in Wuhan in the People's Republic of China, but until now, no study has located the actual source of the virus. Genomic analyses suggest that bat is the most likely origin of this virus (Zhou et al., 2020). The virus has been detected from the pangolins, but there is no concrete evidence that this animal can act as an intermediate host (Lam et al., 2020). Currently, very limited data is available that evaluates the susceptibility of the domestic and wildlife stocks for SARS‐CoV‐2 infection using laboratory testing. There have been reports for positive tests for SARS‐CoV‐2 RNA in cats and ferrets, dogs, minks, golden hamster, rhesus monkey, tigers, and lions (Imai et al., 2020; Kim et al., 2020; Shi et al., 2020; United States Department of Agriculture [USDA], 2020; Yu et al., 2020). Cats do show disease symptoms and transmit the infection to other animals of their species (Shi et al., 2020). In all the cases of pet or zoo animals testing positive, the source of infection was either confirmed or suspected to be a human (American Veterinary Medical Association, 2020).

SARS‐CoV‐2 infection in humans depends on the binding of its spike protein to a human cell receptor angiotensin‐converting enzyme 2 (ACE2) which is expressed across the animal species as a cell surface receptor (Bibiana et al., 2020). Evolutionary conservation of protein sequence of ACE2 across vertebrate species, and more specifically, in hominids and primates, remains strong plausibility (Braun et al., 2020). Recent studies have decoded the receptor‐binding domain (RBD) of SARS‐CoV‐2 spike protein and demonstrated its structural binding with the N‐terminal peptidase domain of human ACE2 (hACE2). Receptor‐binding motif (RBM) on SARS‐CoV‐2 RBD makes direct contacts with amino acid residues at hACE2 (Lan et al., 2020; Wan et al., 2020). We assumed that a homology to hACE2, more particularly to viral RBD‐binding interface, of ACE2 protein sequences of animal species could be used in predicting their susceptibility for contracting SARS‐CoV‐2 infection.

2. MATERIALS AND METHODS

The complete protein sequence of hACE2 (Q9BYF1.2) was retrieved from the open‐access protein sequence data base Uniprot.org. Crystal structures of hACE2 and SARS‐CoV‐2 RBD were created based on X‐RAY diffraction data retrieved from RCSB protein data bank, PBD1D‐6M0J (https://www.rcsb.org/structure/6m0j) using software: PyMOL built from Schrodinger, Inc. Amino acid residues at hACE2/RBD interface, and conserved RBD‐binding hotspots at hACE2, were annotated in consultation with published literature (Lan et al., 2020; Othman et al., 2020; Wan et al., 2020).

Further, the NCBI protein blast tool (https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastp) was used to analyze open‐access protein sequence data of ACE2 for the species in animal kingdom available at NCBI databases. To minimize the prediction error, a two‐step homology search was performed. First, we performed a comparative analysis of the variability of hACE2 with that of wildlife and domestic animal species in complete protein sequences. The accession numbers of the species which showed significant homology (E value ≤ 0) for the complete sequence were selected for further analysis for the second step. In the second step, we narrowed down our homology search to a subrange of 36–53 amino acid residues of hACE2 (<AEDLFYQSSLASWNYNTN>), which contain conserved hotspots for binding of SARS‐CoV‐2 RBD (Othman et al., 2020). A fixed query cover of 100% was applied for the sequence homology match in the second analysis. The final ACE2 sequence homology scores along with the statistical significance value (E value ≤ 1E−08) were used to determine the susceptibility ranking of the animal for contracting SARS‐CoV‐2 infection. A higher sequence homology score with E‐value closure to zero signified higher susceptibility ranking for the species. Details of NCBI protein blast and statistical methods predicting significance can be consulted at https://www.ncbi.nlm.nih.gov/books/NBK20261/.

3. RESULTS

Figure 1 presents crystal structures of hACE2 and SARS‐CoV‐2 RBD (1a), and shows annotations for conserved RBD‐binding hotspots (1b) and other interacting amino acids (1c) and at the ACE2/RBD interface. Significant alignments of the species‐specific ACE2 orthologous to hACE2 (Accession: Q9BYF1.2) for the complete sequence (Table S1) and a partial sequence at the RBD interface (a subrange of 36–53 amino acid residues) (Figure 1b and Table 1) were noted across the animal kingdom. In the search for complete sequence homology as well as a subrange of 36–53 amino acid residues at the RBD interface, hominids and other primates showed the highest homology (up to 100%) with hACE2, followed by carnivores (up to 94.4%), rodents (up to 94.4%), and artiodactyles (even‐toed ungulates) (up to 94.4%). Oxen, water buffaloes, goats, pigs, birds, fishes, and snakes showed no significant match in either of the searches. Sequence homology scores and susceptibility ranking (for contracting SARS‐CoV‐2 infection) for the animal species have been provided in the columns for “Percentage Identity” and "Susceptibility Ranking" in Table 1. The animals which have been described positive for the SARS‐CoV‐2 RNA in the recent literature have been marked (Table 1, footnoteb). ACE2 sequence alignment data for the complete and partial sequences have been provided as Supporting Information, Files 2 and 3.

Figure 1.

Figure 1

Interaction of SARS‐CoV‐2 receptor‐binding domain RBD with Human ACE2. (a) Human ACE2 (gray)—RBD (red)‐binding interface. (b) Segment of Human ACE2 (magenta) consisting of conserved RBD‐binding hotspots (36–53 aa) at the RBD‐binding interface. (c) Important residues participating in the interactions at Human ACE2 (yellow)‐RBD (cyan) interface. Source: RCSB protein data bank, PBD1D‐6M0J. Software used: PyMOL built by Schrodinger, Inc. [Color figure can be viewed at wileyonlinelibrary.com]

Table 1.

Species‐specific ACE2 sequences producing significant alignments to human ACE2a

Description Order/Family Query cover (%) E value Percentage identity Accession no. Susceptibility ranking
ACE2 (Gorilla gorilla [Gorilla]) Primate/Hominidae 100 2E−16 100 XP_018874749.1 1
ACE2 isoform X1 (Pan troglodytes [Chimpanzee]) Primate/Hominidae 100 2E−16 100 XP_016798468.1 2
ACE2 isoform X1 (Pan paniscus [Bonobo]) Primate/Hominidae 100 2E−16 100 XP_008972428.1 3
ACE2 isoform X1 (Pongoabelii [Sumatran orangutan]) Primate/Hominidae 100 2E−16 100 XP_024096013.1 4
ACE2 (Hylobatesmoloch [Silvery gibbon]) Primate/Hylobatidae 100 2E−16 100 XP_032612508.1 5
ACE2 (Nomascus leucogenys [Northern white‐cheeked gibbon]) Primate/Hylobatidae 100 2E−16 100 XP_003261132.2 6
ACE2 (Piliocolobus tephrosceles [Ugandan red colobus]) Primate/Cercopithecidae 100 2E−16 100 XP_023054821.1 7
ACE2 (Rhinopithecus roxellana [Golden snub‐nosed monkey]) Primate/Cercopithecidae 100 2E−16 100 XP_010364367.2 8
ACE2 (Theropithecus gelada [Gelada]) Primate/Cercopithecidae 100 2E−16 100 XP_025227847.1 9
ACE2 (Papioanubis [Olive baboon]) Primate/Hominidae 100 2E−16 100 XP_021788732.1 10
ACE2 (Macaca nemestrina [Southern pig‐tailed macaque]) Primate/Cercopithecidae 100 2E−16 100 XP_011733505.1 11
ACE2 (Macaca mulatta [Rhesus macaque])b Primate/Cercopithecidae 100 2E−16 100 ACI04556.1 12
PREDICTED: ACE2 (Macaca fascicularis [Crab‐eating macaque]) Primate/Cercopithecidae 100 2E−16 100 XP_005593094.1 13
PREDICTED: ACE2 (Cercocebus atys [Sooty mangabey]) Primate/Cercopithecidae 100 2E−16 100 XP_011891198.1 14
PREDICTED: ACE2 (Mandrillus sphinx [Mandrill]) Primate/Cercopithecidae 100 2E−16 100 XP_011850923.1 15
PREDICTED: ACE2 (Chlorocebus sabaeus [Green monkey]) Primate/Cercopithecidae 100 2E−16 100 XP_007989304.1 16
ACE2 (Ursusarctos horribilis [Grizzly bear]) Carnivora/Ursidae 100 2E−15 94.44 XP_026333865.1 17
PREDICTED: ACE2 (Ailuropoda melanoleuca  (Giant panda]) Carnivora/Ursidae 100 2E−15 94.44 XP_002930657.1 18
PREDICTED: ACE2 (Ursus maritimus [Polar bear]) Carnivora/Ursidae 100 2E−15 94.44 XP_008694637.1 19
PREDICTED: ACE2 isoform X1 (Chinchilla lanigera [Long‐tailed chinchilla]) Rodentia/Chinchillidae 100 3E−14 94.44 XP_013362428.1 20
ACE2 (Heterocephalus glaber [Naked mole‐rat]) Rodentia/Heterocephalidae 100 3E−14 94.44 XP_004866157.1 21
ACE2 (Camelusferus [Wild Bactrian camel]) Artiodactyla/Camelidae 100 3E−14 94.44 XP_006194263.1 22
PREDICTED: ACE2 (Jaculus jaculus [Lesser Egyptian jerboa]) Rodentia/Dipodidae 100 3E−14 94.44 XP_004671523.1 23
PREDICTED: ACE2 isoform X1 X1 (Dipodomys ordii [Ord's kangaroo rat]) Rodentia/Heteromyidae 100 3E−14 94.44 XP_012887572.1 24
ACE2 (Physeter catodon [Sperm whale]) Artiodactyla/Physeteridae 100 3E−14 94.44 XP_023971279.1 25
ACE2 (Lipotes vexillifer [baiji]) Artiodactyla/Lipotidae 100 3E−14 94.44 XP_007466389.1 26
ACE2 (Octodon degus [Common degu]) Rodentia/Octodontidae 100 3E−13 88.89 XP_023575315.1 27
ACE2 (Eumetopias jubatus [Steller sea lion]) Carnivora/Otariidae 100 3E−13 88.89 XP_027970822.1 28
PREDICTED: ACE2 (Fukomys damarensis [Damara land Mole‐rat]) Rodentia/Bathyergidae 100 3E−13 88.89 XP_010643477.1 29
ACE2 (Puma concolor [Cougar]) Carnivora/Felidae 100 3E−13 88.89 XP_025790417.1 30
PREDICTED: ACE2 isoform X1 (Pantherapardus [Leopard]) Carnivora/Felidae 100 3E−13 88.89 XP_019273508.1 31
ACE2 isoform X1 (Acinonyx jubatus [Cheetah]) Carnivora/Felidae 100 3E−13 88.89 XP_026910297.1 32
ACE2 precursor (Felis catus [Cat])b Carnivora/Felidae 100 3E−13 88.89 NP_001034545.1 33
ACE2 (Lynx pardinus [Iberian lynx]) Carnivora/Felidae 100 3E−13 88.89 VFV30336.1 34
ACE2 (Lynx canadensis [Canada lynx]) Carnivora/Felidae 100 3E−13 88.89 XP_030160839.1 35
ACE2 (Mesocricetus auratus [Golden hamster])b Rodentia/Cricetidae 100 3E−13 88.89 XP_005074266.1 36
ACE2 (Cricetulus griseus [Chinese hamster]) Rodentia/Cricetidae 100 3E−13 88.89 XP_003503283.1 37
ACE2 (Manis javanica [Sunda pangolin]) Pholidota/Manidae 100 3E−13 88.89 XP_017505746.1 38
ACE2 (Peromyscus bairdii [North American deer mouse]) Rodentia/Cricetidae 100 3E−13 88.89 XP_006973269.1 39
ACE2 (Microtus ochrogaster [Prairie vole]) Rodentia/Cricetidae 100 3E−3 88.89 XP_005358818.1 40
PREDICTED: ACE2 (Panthera tigris (Tiger])b Carnivora/Felidae 100 3E−13 88.89 XP_007090142.1 41
PREDICTED: ACE2 (Panthera leo [lion]) Carnivora/Felidae 100 3E−13 88.89 Query_32935c 42
ACE2 (Balaenoptera acutorostrata [Minke whale]) Cetartiodactyla/Balaenopteridae 100 1E−12 88.89 XP_028020351.1 43
PREDICTED: ACE2 (Saimiri boliviensi [Black‐capped squirrel monkey]) Primate/Cebidae 100 1E−12 83.33 XP_010334925.1 44
ACE2 (Sapajus apella [Tufted capuchin]) Primate/Cebidae 100 1E−12 83.33 XP_032141854.1 45
PREDICTED: ACE2 (Cebus capucinus [Panamanian White‐faced Capuchin]) Primate/Cebidae 100 1E−12 83.33 XP_017367865.1 46
ACE2 (Aotusnancymaae [Nancy Ma's night monkey]) Primate/Aotidae 100 1E−12 83.33 XP_012290105.1 47
ACE2 (Callithrix jacchus [Common marmoset]) Primate/Callitrichidae 100 1E−12 83.33 XP_008987241.1 48
ACE2 (Carlito syrichta [Philippine tarsier]) Primate/Tarsiidae 100 1E−12 83.33 XP_008062810.1 49
PREDICTED: ACE2 (Propithecus coquereli [Coquerel's sifaka]) Primate/Indriidae 100 2E−12 83.33 XP_012494185.1 50
PREDICTED: ACE2 (Oryctolagus cuniculus [European rabbit]) Lagomorpha/Leporidae 100 2E−12 83.33 XP_002719891.1 51
ACE2 (Mustel aerminea [Stoat]) Carnivora/Mustelidae 100 2E−12 83.33 XP_032187677.1 52
ACE2 (Mustela putorius furo [European domestic ferret])b Carnivora/Mustelidae 100 2E−12 83.33 Q2WG88 53
PREDICTED: ACE2 (Ceratotherium simum [White rhinoceros]) Perissodactyla/Rhinocerotidae 100 4E−12 83.33 XP_004435206.1 54
ACE2 (Vicugnapacos [Alpaca]) Cetartiodactyla/Camelidae 100 6E−12 88.89 XP_006212709.1 55
ACE2 Isoform XI (Canis lupus familiaris [Dog])b Carnivora/Canidae 100 6E−12 83.33 XP_005641049.1 56
PREDICTED: ACE2 (Marmota marmota [Alpine marmot]) Rodentia/Sciuridae 100 2E−11 88.89 XP_015343540.1 57
ACE2 (Marmota flaviventris [Yellow‐bellied marmot]) Rodentia/Sciuridae 100 2E−11 88.89 XP_027802308.1 58
PREDICTED: ACE2 (Ochotonaprinceps [American pika]) Lagomorpha/Ochotonidae 100 2E−11 77.78 XP_004597549.2 59
ACE2 (Paguma larvata [Masked palm civet]) Carnivora/Viverridae 100 6E−11 77.78 Q56NL1.1 60
ACE2 (Ictidomys tridecemlineatus [Thirteen‐lined ground squirrel]) Rodentia/Sciuridae 100 1E−10 83.33 XP_005316051.3 61
ACE2 isoform X1 (Myotis lucifugus (Little brown bat]) Chiroptera/Vespertilionidae 100 2E−10 77.78 XP_023609437.1 62
PREDICTED: ACE2 (Equus przewalskii [Przewalski's horse]) Perissodactyla/Equidae 100 3E−10 77.78 XP_008542995.1 63
ACE2 (Equus caballus [Horse]) Perissodactyla/Equidae 100 3E−10 77.78 XP_001490241.1 64
ACE2 enzyme (Crocuta crocuta [Spotted hyena]) Carnivora/Hyaenidae 100 6E−09 72.22 KAF0878287.1 65
ACE2 isoform X1 (Urocitellus parryii [Arctic ground squirrel]) Rodentia/Sciuridae 100 1E−08 77.78 XP_026252505.1 66

Note: hACE2 Accession no.: Q9BYF1.2; query subrange: 36–53aa; subject subrange: 36–53aa.

a

Species/Family compared: Primates (taxid: 9443), cat family (taxid: 9681), Equus (taxid: 9789), ferret (taxid: 9669), dog, coyote, wolf, fox (taxid: 9608), elephants (taxid: 9779), oxen, cattle (taxid: 9903), water buffalo (taxid: 89462), goats (taxid: 9925), pigs (taxid: 9821), deer (taxid: 9850), lion (taxid: 9689), Ursidae (taxid: 9632), Camelidae (taxid: 9835), carnivores (taxid: 33554), Mammalia (taxid: 40674), Rodents and rabbits (taxid: 314147), house mouse (taxid: 10090), birds (taxid: 8782), fishes (taxid: 7898), snakes (taxid: 8570), mouse (taxid: 10088), bats (taxid: 9397).

b

SARS‐CoV‐2 RNA testing positive (Imai et al., 2020; Kim et al., 2020; Shi et al., 2020; United States Department of Agriculture [USDA], 2020; Yu et al., 2020).

c

ACE2 protein sequence for Panthera leo (Lion) is not available in NCBI data base. A predicted ACE2 sequence has been referred from Alexander et al. (2020).

4. DISCUSSION

Zoonotic spillover of human infectious diseases is not uncommon. Recent reports of SARS‐CoV‐2 infection and COVID‐19 symptoms in selected wildlife and domestic animals warranted for caution that the epidemic can have possible spread in animal settings like zoos and wildlife sanctuaries, including a threat of viral transmission from domestic animals (CDC, 2020; Tiwari et al., 2020; Yoo & Yoo, 2020). The species‐specific protein sequence homology to hACE2 may be a valuable tool for predicting susceptibility for contracting SARS‐CoV‐2 infection. It can be used as a screening tool for guiding viral RNA‐based laboratory testing to contain COVID‐19 spread in wildlife and domestic animals during an epidemic outbreak.

Currently, polymerase chain reaction (PCR)‐based laboratory testing for SARS‐CoV‐2 RNA is a standard practice for detecting viral infection and development of COVID‐19 in humans. However, viral infectivity studies involving animals, especially wildlife, are very limited for now. We used open‐access bioinformatics tools to predict susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals. For this purpose, we performed a comparative analysis of the variability of complete protein sequence and SARS‐CoV‐2 RBD‐binding hotspots of hACE2 with that of the animal species. On the basis of the sequence homology, we predicted the highest susceptibility for hominids and other primates, followed by carnivores, rodents, and artiodactyles (ungulates), however, sequence match varied widely among the species in any order of the animal kingdom. A similar pattern of susceptibility prediction was recently reported by Damas et al., (2020) who compared ACE2 sequence homology across species, however, their species list varied from us, which can be explained by differences of data sources. Damas et al., (2020) also noted conservation of ACE2 protein sequence among evolutionarily linked species; this has been reflected in our study also, as we find the highest sequence homology to hACE2 in the members of order hominids and primate who are closest to humans, and further across mammalians, and other categories of vertebrates. A lesser sequence homology was found with the species which are remotely related to humans.

Our susceptibility predictions for cats, dogs, golden hamster, rhesus monkey, tigers, and lions get confirmation from the recent reports in literature which had performed PCR‐based laboratory testing for SARS‐CoV‐2 RNA in the selective animals (Table 1, footnoteb) (Imai et al., 2020; Kim et al., 2020; Shi et al., 2020; United States Department of Agriculture USDA, 2020; Yu et al., 2020). However, a viral RNA‐based susceptibility information is currently highly limited, especially for the animals inhabiting in natural settings.

For certain species, such as American mink and ferret, which was recently reported to get SARS‐CoV‐2 infection (Shi et al., 2020; USDA, 2020); although we found their significant homology to hACE2 (Table S1), we couldn't get homology score for SARS‐CoV‐2 RBD‐binding hotspots in absence of complete protein sequence of ACE2 for these species. However, we found significant homology for SARS‐CoV‐2 RBD‐binding hotspots for the species which are closely related to them, such as, European mink and stoat for which the complete protein sequences for ACE2 were available (Table 1).

Our two‐step comparison for sequence homology (for complete sequence and SARS‐CoV‐2 RBD‐binding hotspots, respectively) has reduced the chances of false inclusions and provides a susceptibility rank which may help to identify the most vulnerable animal species for contracting SARS‐CoV‐2 infection. Many of the wild animals noted in the list, such as giant panda, white rhinoceros, are endangered, which raises immediate concern to protect them from the reach of the COVID‐19 pandemic. Laboratory testing of viral RNA for wildlife animals in zoos and sanctuaries is limited by many practical factors, in that sense software‐based tool to predict COVID‐19 susceptibility in the animals presents a very easy and cheap option for COVID‐19 prevention and containment in these settings. However, there remains a need to further confirm their susceptibility through laboratory testing of viral RNA.

4.1. Limitations

In the present study, we considered only viral host cell entry receptor ACE2 homology for predicting the susceptibility, however, SARS‐CoV‐2 host cell entry and replication, in addition, may also depend on many other factors like tissue proteases TMPRSS2 or CTSL, and ADAM‐17 (Zhang et al., 2020), thus, a hACE2 homology may not be sufficient, and a viral infectivity testing of the listed animals will be necessary to confirm their susceptibility for contracting SARS‐CoV‐2 infection. Also, some animals may not develop clinical symptoms or transmit the virus even after contracting SARS‐CoV‐2 infection, hence their identification through viral RNA testing accompanied by clinical observation will be necessary to understand their susceptibility risk.

Additionally, our susceptibility prediction list (Table 1) has only provided an assessment for the animal species for which ACE2 protein sequence (more particularly from amino acid residues 36–53) is available in the NCBI data base (except, Panthera leo, for which ACE2 sequence has been referred from Alexander et al., 2020). However, this tool can be suitably used to screen remaining animals if their ACE2 protein sequence is made available.

CONFLICT OF INTERESTS

The authors declare that there are no conflict of interests.

Supporting information

Supporting information.

Supporting information.

Supporting information.

Kumar A, Pandey SN, Pareek V, Narayan RK, Faiq MA, Kumari C. Predicting susceptibility for SARS‐CoV‐2 infection in domestic and wildlife animals using ACE2 protein sequence homology. Zoo Biology. 2021;40:79–85. 10.1002/zoo.21576

DATA AVAILABILITY STATEMENT

Sequence alignment data generated in this study have been provided as Supporting Information Files 2 and 3. ACE2 protein sequences used for this study can be retrieved from NCBI protein (https://www.ncbi.nlm.nih.gov/protein) and Uniprot.org (https://www.uniprot.org/) databases using species‐specific accession numbers provided in Tables 1 and S1.

REFERENCES

  1. American Veterinary Medical Association . (2020). SARS‐CoV‐2 in animals. AVMA. https://www.avma.org/resources-tools/animal-health-and-welfare/covid-19/sars-cov-2-animals-including-pets
  2. Alexander, M. R. , Schoeder, C. T. , Brown, J. A. , Smart, C. D. , Moth, C. , Wikswo, J. P. , Capra, J. A. , Meiler, J. , Chen, W. , & Madhur, M. S. (2020). Which animals are at risk? Predicting species susceptibility to Covid‐19. bioRxiv: the preprint server for biology. 10.1101/2020.07.09.194563 [DOI] [Google Scholar]
  3. Braun, M. , Sharon, E. , Unterman, I. , Miller, M. , Shtern, A. M. , Benenson, S. , Vainstein, A. , & Tabach, Y. (2020). ACE2 co‐evolutionary pattern suggests targets for pharmaceutical intervention in the COVID‐19 pandemic. iScience, 23(8), 101384. 10.1016/j.isci.2020.101384 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bibiana, S. O. F. , Vargas‐Pinilla, P. , Amorim, C. , Sortica, V. A. , & Bortolini, M. C. (2020). ACE2 diversity in placental mammals reveals the evolutionary strategy of SARS‐CoV‐2. Genetics and Molecular Biology, 43(2), e20200104. 10.1590/1678-4685-gmb-2020-0104 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CDC . (2020). COVID‐19 and animals. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/animals.html
  6. Damas, J. , Hughes, G. M. , Keough, K. C. , Painter, C. A. , Persky, N. S. , Corbo, M. , Hiller, M. , Koepfli, K. P. , Pfenning, A. R. , Zhao, H. , Genereux, D. P. , Swofford, R. , Pollard, K. S. , Ryder, O. A. , Nweeia, M. T. , Lindblad‐Toh, K. , Teeling, E. C. , Karlsson, E. K. , & Lewin, H. A. (2020). Broad host range of SARS‐CoV‐2 predicted by comparative and structural analysis of ACE2 in vertebrates. Proceedings of the National Academy of Sciences of the United States of America, 117(36), 22311–22322. 10.1073/pnas.2010146117 [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Imai, M. , Iwatsuki‐Horimoto, K. , Hatta, M. , Loeber, S. , Halfmann, P. J. , Nakajima, N. , Watanabe, T. , Ujie, M. , Takahashi, K. , Ito, M. , Yamada, S. , Fan, S. , Chiba, S. , Kuroda, M. , Guan, L. , Takada, K. , Armbrust, T. , Balogh, A. , Furusawa, Y. , … Kawaoka, Y. (2020). Syrian hamsters as a small animal model for SARS‐CoV‐2 infection and countermeasure development. Proceedings of the National Academy of Sciences of the United States of America, 117(28), 16587–16595. 10.1073/pnas.2009799117 [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kim, Y. I. , Kim, S. G. , Kim, S. M. , Kim, E. H. , Park, S. J. , Yu, K. M. , Chang, J. H. , Kim, E. J. , Lee, S. , Casel, M. A. B. , Um, J. , Song, M. S. , Jeong, H. W. , Lai, V. D. , Kim, Y. , Chin, B. S. , Park, J. S. , Chung, K. H. , Foo, S. S. , … Choi, Y. K. (2020). Infection and Rapid Transmission of SARS‐CoV‐2 in Ferrets. Cell Host and Microbe, 27(5), 704–709. 10.1016/j.chom.2020.03.023 [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Lan, J. , Ge, J. , Yu, J. , Shan, S. , Zhou, H. , Fan, S. , Zhang, Q. , Shi, X. , Wang, Q. , Zhang, L. , & Wang, X. (2020). Structure of the SARS‐CoV‐2 spike receptor‐binding domain bound to the ACE2 receptor. Nature, 581(7807), 215–220. 10.1038/s41586-020-2180-5 [DOI] [PubMed] [Google Scholar]
  10. Lam, T. T. Y. , Shum, M. H. H. , Zhu, H. C. , Tong, Y. G. , Ni, X. B. , Liao, Y. S. , & Guan, Y. (2020). Identifying SARS‐CoV‐2 related coronaviruses in Malayan pangolins. Nature, 1–4. 10.1038/s41586-020-2169-0 [DOI] [PubMed] [Google Scholar]
  11. Othman, H. , Bouslama, Z. , Brandenburg, J. T. , Da Rocha, J. , Hamdi, Y. , Ghedira, K. , Srairi‐Abid, N , & Hazelhurst, S. (2020). Interaction of the spike protein RBD from SARS‐CoV‐2 with ACE2: similarity with SARS‐CoV, hot‐spot analysis and effect of the receptor polymorphism. Biochemical and Biophysical Research Communications, 527(3), 702–708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shi, J. , Wen, Z. , Zhong, G. , Yang, H. , Wang, C. , Huang, B. , Liu, R. , He, X. , Shuai, L. , Sun, Z. , Zhao, Y. , Liu, P. , Liang, L. , Cui, P. , Wang, J. , Zhang, X. , Guan, Y. , Tan, W. , Wu, G. , … Bu, Z. (2020). Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS‐coronavirus 2. Science (New York, N.Y.), 368(6494), 1016–1020. 10.1126/science.abb7015 [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Tiwari, R. , Dhama, K. , Sharun, K. , Iqbal Yatoo, M. , Malik, Y. S. , Singh, R. , Michalak, I. , Sah, R. , Bonilla‐Aldana, D. K. , & Rodriguez‐Morales, A. J. (2020). COVID‐19: animals, veterinary and zoonotic links. Veterinary Quarterly, 40(1), 169–182. 10.1080/01652176.2020.1766725 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. United States Department of Agriculture (USDA) . (2020, September) Confirmed cases of SARS‐CoV‐2 in Animals in the United States. USDA. https://www.aphis.usda.gov/aphis/ourfocus/animalhealth/sa_one_health/sars-cov-2-animals-us
  15. Wan, Y. , Shang, J. , Graham, R. , Baric, R. S. , & Li, F. (2020). Receptor recognition by the novel coronavirus from Wuhan: An analysis based on decade‐long structural studies of SARS coronavirus. Journal of Virology, 94(7), e00127–e00220. 10.1128/jvi.00127-20 [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Yoo, H. S. , & Yoo, D. (2020). COVID‐19 and veterinarians for one health, zoonotic‐ and reverse‐zoonotic transmissions. Journal of Veterinary Science, 21(3), e51. 10.4142/jvs.2020.21.e51 [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Yu, P. , Qi, F. , Xu, Y. , Li, F. , Liu, P. , Liu, J. , Bao, L. , Deng, W. , Gao, H. , Xiang, Z. , Xiao, C. , Lv, Q. , Gong, S. , Liu, J. , Song, Z. , Qu, Y. , Xue, J. , Wei, Q. , Liu, M. , … Qin, C. (2020). Age‐related rhesus macaque models of COVID‐19. Animal Models and Experimental Medicine, 3(1), 93–97. 10.1002/ame2.12108 [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Zhou, P. , Yang, X. L. , Wang, X. G. , Hu, B. , Zhang, L. , Zhang, W. , Si, H. R. , Zhu, Y. , Li, B. , Huang, C. L. , Chen, H. D. , Chen, J. , Luo, Y. , Guo, H. , Jiang, R. D. , Liu, M. Q. , Chen, Y. , Shen, X. R. , Wang, X. , … Shi, Z. L. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. 10.1038/s41586-020-2012-7 [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zhang, H. , Rostami, M. R. , Leopold, P. L. , Mezey, J. G. , O'Beirne, S. L. , Strulovici‐Barel, Y. , & Crystal, R. G. (2020). Expression of the SARS‐CoV‐2 ACE2 receptor in the human airway epithelium. American Journal of Respiratory and Critical Care Medicine, 202(2), 219–229. 10.1164/rccm.202003-0541OC [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supporting information.

Supporting information.

Supporting information.

Data Availability Statement

Sequence alignment data generated in this study have been provided as Supporting Information Files 2 and 3. ACE2 protein sequences used for this study can be retrieved from NCBI protein (https://www.ncbi.nlm.nih.gov/protein) and Uniprot.org (https://www.uniprot.org/) databases using species‐specific accession numbers provided in Tables 1 and S1.


Articles from Zoo Biology are provided here courtesy of Wiley

RESOURCES