Abstract
Simple SummarySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic COVID-19. The virus infects human cells by binding of the virus spike to the cell receptor ACE2. Some studies suggest that dogs, cats and other animal species could be infected by SARS-CoV-2, while very limited data are available on lagomorphs. There are several occasions where rabbits and other lagomorphs are in close contact with humans. To investigate the interaction between SARS-CoV-2 spikes and ACE2 of lagomorphs, predictive computer-based models were used in this study. The structure of ACE2 of lagomorphs was obtained on the basis of the amino acid sequences computationally. The interaction with the model of SARS-CoV-2 spikes was studied and described in depth on the basis of the complex human ACE2-SARS-CoV-2 published before. The interaction among SARS-CoV-2 spikes and ACE2 of other companion or laboratory animals is also described for comparative purposes. The results predict that ACE2 of lagomorphs are likely to bind SARS-CoV-2 spikes and suggest that further studies would be justified to confirm these results and to evaluate the risks to humans being in close contact with lagomorphs, such as veterinarians, farmers, slaughterhouse workers, butchers or pet owners.Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic COVID-19. The virus infects human cells by binding of the virus spike to the cell receptor ACE2. The crystal structure of SARS-CoV-2 spikes in complex with human ACE2 has recently been solved, and the main amino acid residues involved in the virus–receptor complex have been detected. To investigate the affinity of ACE2 of lagomorphs to the SARS-CoV-2 spike, ACE2 sequences from rabbits and American pikas were compared with human ACE2 and with ACE2 from mammals with different susceptibility to the virus. Models of the complex formed by SARS-CoV-2 spike and ACE2 from lagomorphs and from other mammals were created for comparative studies. ACE2 of lagomorphs showed fewer substitutions than human ACE2 in residues involved in the ACE2-SARS-CoV-2 spike complex, similar to cats. Analysis of the binding interface of the simulated complexes ACE2-SARS-CoV-2 spike showed high affinity of the ACE2 of lagomorphs to the viral spike protein. These findings suggest that the spike of SARS-CoV-2 could bind the ACE2 receptor of lagomorphs, and future studies should investigate the role of lagomorphs in SARS-CoV-2 epidemiology. Furthermore, the risks to humans coming into close contacts with these animals should be evaluated.
Highlights
Since its discovery in China, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly worldwide, causing the Coronavirus Disease 2019 (COVID-19) pandemic [1].severe acute respiratory syndrome (SARS)-CoV-2 belongs to the genus Betacoronavirus and shows very high sequence similarity to bat Rhinolophus affinis coronavirus RaTG13 in the whole genome (93.7% amino acid similarity) [2] and to the Guangdong pangolin coronaviruses in the receptor-binding domain (RBD) [3,4]
Not all angiotensin-converting enzyme 2 (ACE2) amino acids are involved in the complex with SARS-CoV-2-RBD, being only 22 residues involved in the binding with SARS-CoV-2-RBD [6]
The predicted protein–protein complex ∆G in rabbits is the same as in humans. These findings suggest that SARS-CoV-2-RBD could bind ACE2 receptor of rabbits and American pikas to in humans, these findings need to be confirmed
Summary
Since its discovery in China, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly worldwide, causing the Coronavirus Disease 2019 (COVID-19) pandemic [1].SARS-CoV-2 belongs to the genus Betacoronavirus and shows very high sequence similarity to bat Rhinolophus affinis coronavirus RaTG13 in the whole genome (93.7% amino acid similarity) [2] and to the Guangdong pangolin coronaviruses in the receptor-binding domain (RBD) [3,4]. Since its discovery in China, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading rapidly worldwide, causing the Coronavirus Disease 2019 (COVID-19) pandemic [1]. RBD is part of the C-terminal domain of the S1 subunit in the SARS-CoV-2 spike protein (S), which interacts with the human angiotensin-converting enzyme 2 (hACE2) receptor [5,6]. Priming of coronavirus spike proteins by host cell proteases is essential for viral entry into cells. Despite other entry mechanisms and potential receptors are under investigations [10,11], the angiotensin-converting enzyme 2 (ACE2) is considered the main receptor for SARS-CoV2 so far. HACE2 is the receptor of the other Betacoronavirus SARS-CoV, which caused the severe acute respiratory syndrome (SARS) epidemic in 26 countries in 2002–2003 [13] ACE2 protein is abundantly expressed in different cells of the human respiratory tract, and in many other cells in several organs [12]. hACE2 is the receptor of the other Betacoronavirus SARS-CoV, which caused the severe acute respiratory syndrome (SARS) epidemic in 26 countries in 2002–2003 [13]
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