The molecular basis for SARS-CoV-2 binding to dog ACE2

Zhang, Zengyuan; Zhang, Yanfang; Liu, Kefang; Li, Yan; Lu, Qiong; Wang, Qingling; Zhang, Yuqin; Wang, Liang; Liao, Hanyi; Zheng, Anqi; Ma, Sufang; Fan, Zheng; Li, Huifang; Huang, Weijin; Bi, Yang; Zhao, Xin; Wang, Qihui; Gao, George F.; Xiao, Haixia; Tong, Zhou; Qi, Jianxun; Sun, Yeping

doi:10.1038/s41467-021-24326-y

Cited by 49 publications

(49 citation statements)

References 48 publications

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“…This can be explained by the missing N-terminal residues (M, Q, S, T which are solved in the crystal structure) in the predicted model, the position and orientation of E22 and D23 (as the terminal residues in the predicted model) were affected during the MD refinement. However, these weakened interactions are also in line with the reported experimental binding affinities of dACE2 ( K D = 123 nM) to RBD as compared to the hACE2 (K D = 18.5 nM) [ 41 ]. Horse ACE2 forms only 3 hydrogen bonds with RBD ( Fig.…”

Section: Resultssupporting

confidence: 85%

“…The dog ACE2 (dACE2) contains a notable variation at N-terminal-helix 1 which results in gapping (deletion) at position 20, revealed in the sequence alignment. While this deletion does not appear to affect the complex structure revealed in the homology model, it slightly differs from the crystal structure of dACE2-RBD that has been solved [ 41 ]. In the case of our homology model of dACE2-RBD ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain

Lupala

Kumar

et al. 2022

Computers in Biology and Medicine

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Section: Resultssupporting

confidence: 85%

Section: Resultsmentioning

confidence: 99%

Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain

Lupala

Kumar

et al. 2022

Computers in Biology and Medicine

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“…Consistent with the reciprocal experiment in mice described above ( Fig 2E ), RBD binding to the ACE2 of both human and dog was abolished with just these 6 mouse substitutions ( Fig 2J and 2K ). This is surprising given the numerous other sites implicated in mediating human and dog ACE2 interactions with the viral RBD [ 23 , 25 , 63 ]. In both human and dog ACE2, abolition of RBD binding depended on mutating sites 24 and 82 ( Fig 2J and 2K ), despite displaying different residues in human (Q24; M82) and dog (L24; T82) ACE2 ( Fig 2C ).…”

Section: Resultsmentioning

confidence: 99%

Evolutionary pathways to SARS-CoV-2 resistance are opened and closed by epistasis acting on ACE2

Castiglione

Zhou

et al. 2021

PLoS Biol

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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infects a broader range of mammalian species than previously predicted, binding a diversity of angiotensin converting enzyme 2 (ACE2) orthologs despite extensive sequence divergence. Within this sequence degeneracy, we identify a rare sequence combination capable of conferring SARS-CoV-2 resistance. We demonstrate that this sequence was likely unattainable during human evolution due to deleterious effects on ACE2 carboxypeptidase activity, which has vasodilatory and cardioprotective functions in vivo. Across the 25 ACE2 sites implicated in viral binding, we identify 6 amino acid substitutions unique to mouse—one of the only known mammalian species immune to SARS-CoV-2. Substituting human variants at these positions is sufficient to confer binding of the SARS-CoV-2 S protein to mouse ACE2, facilitating cellular infection. Conversely, substituting mouse variants into either human or dog ACE2 abolishes viral binding, diminishing cellular infection. However, these same substitutions decrease human ACE2 activity by 50% and are predicted as pathogenic, consistent with the extreme rarity of human polymorphisms at these sites. This trade-off can be avoided, however, depending on genetic background; if substituted simultaneously, these same mutations have no deleterious effect on dog ACE2 nor that of the rodent ancestor estimated to exist 70 million years ago. This genetic contingency (epistasis) may have therefore opened the road to resistance for some species, while making humans susceptible to viruses that use these ACE2 surfaces for binding, as does SARS-CoV-2.

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“…[ 2 ] demonstrated experimentally that cats and ferrets are susceptible to SARS-CoV-2, but poorly replicates in dogs, chickens, ducks, and pigs. The general structures of the receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (dACE2) of dogs are similar to the human RBD/ACE2 complex; however, the interaction of the two complexes is different, justifying the difficulty of viral replication in this species [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Retrospective surveillance of severe acute respiratory syndrome coronavirus 2 in pets from Brazil

Carvalho¹,

Ristow²,

Rodrigues

et al. 2021

Vet World

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Background and Aim: The emerging concerns regarding the new Coronavirus's ability to cause infection in pets has led to animal testing and worrisome findings reported all over the world in domesticated and wild animals. This study aimed to investigate severe acute respiratory syndrome coronavirus (SARS-CoV)-2 by quantitative reverse transcription-polymerase chain reaction in dog and cat samples with the clinical presentation for respiratory or gastrointestinal disease in Brazil. Materials and Methods: One hundred and twenty-five samples were collected from 12 states of Brazil that originated from the gastrointestinal, upper respiratory tract, and other sites, including some pools of samples from before the onset of the pandemic including blood and/or urine samples. They were tested for RT-PCR detection of respiratory or gastrointestinal pathogens through Respiratory or Diarrhea RT-PCR Panels in the TECSA (Tecnologia em Saninade Animal - Animal Health Technology) Veterinary Medicine Laboratory. This work was conducted in compliance with ethical standards. Results: Seven different microorganisms that can cause respiratory and/or gastrointestinal clinical signs were detected in cats (Feline Coronavirus [FCoV], Feline Parvovirus, Feline Leukemia Virus, Feline Calicivirus, Mycoplasma felis, Campylobacter spp., and Cryptosporidium spp.) and three in dogs (canine distemper virus, Cryptosporidium spp., and Babesia spp.). Conclusion: Although the samples corresponded to the beginning of coronavirus disease-19 spread in Brazil and clinically correlated with the expected viral replication sites, none of the animals tested positive for SARS-CoV-2; reassuringly, four cats tested positive or FCoV none of them were positive for SARS-CoV2. The epidemiological surveillance of SARS-CoV-2 in pets is considered a one health issue, important for monitoring the disease evolution, spread and minimizing the animal-human health impacts, and directing Public Health Policies.

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The molecular basis for SARS-CoV-2 binding to dog ACE2

Cited by 49 publications

References 48 publications

Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain

Computational insights into differential interaction of mammalian angiotensin-converting enzyme 2 with the SARS-CoV-2 spike receptor binding domain

Evolutionary pathways to SARS-CoV-2 resistance are opened and closed by epistasis acting on ACE2

Retrospective surveillance of severe acute respiratory syndrome coronavirus 2 in pets from Brazil

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