Abstract
SARS-CoV-2 can infect many domestic animals, including dogs. Herein, we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. We solved the crystal structure of RBD in complex with dACE2 and found that the total number of contact residues, contact atoms, hydrogen bonds and salt bridges at the binding interface in this complex are slightly fewer than those in the complex of the RBD and human ACE2 (hACE2). This result is consistent with the fact that the binding affinity of RBD to dACE2 is lower than that of hACE2. We further show that a few important mutations in the RBD binding interface play a pivotal role in the binding affinity of RBD to both dACE2 and hACE2. Our work reveals a molecular basis for cross-species transmission and potential animal spread of SARS-CoV-2, and provides new clues to block the potential transmission chains of this virus.
Highlights
SARS-CoV-2 can infect many domestic animals, including dogs
receptor binding domain (RBD) is responsible for receptor recognition, which had been mapped to the C-terminal domain (CTD) in previous structural studies9,10. dog angiotensin-converting enzyme 2 (dACE2) shares 83.88% primary sequence identity with human angiotensinconverting enzyme 2 (ACE2) (hACE2)
The results showed that the dissociation constant (KD) between RBD and hACE2 was 18.5 nM, while that between RBD and dACE2 was 123 nM, which confirms that dACE2 can bind to RBD, but with a binding affinity 6.65 times lower than that of hACE2 (Fig. 1b and c)
Summary
SARS-CoV-2 can infect many domestic animals, including dogs. we show that dog angiotensin-converting enzyme 2 (dACE2) can bind to the SARS-CoV-2 spike (S) protein receptor binding domain (RBD), and that both pseudotyped and authentic SARS-CoV-2 can infect dACE2-expressing cells. Dogs from households with confirmed human cases of COVID-19 in Hong Kong were confirmed to be infected with SARS-CoV-2, and the genetic sequences of the viruses from two dogs were identical to that of the viruses detected in the respective human cases Evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-211. A large-scale epidemiological survey that included 919 cats and dogs living in Italy showed that 3.3% of dogs and 5.8% of cats were SARS-CoV-2 neutralizing antibody positive, and dogs from COVID-19 positive households were significantly more likely to test positive than those from COVID-19-negative households[12] These results further stress the potential risk of these pets in the spread of SARSCoV-2
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