The devastating impact of the COVID19 pandemic caused by SARS coronavirus 2 ( SARSCoV2 ) has raised important questions on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals to humans, whether companion animals or those used for commercial purposes can act as reservoirs for infection, and the reasons for the large variations in  susceptibilities across animal species. Traditional lab-based methods will ultimately answer many of these questions but take considerable time. In silico modeling methods provide the opportunity to rapidly generate information on newly emerged pathogens to aid countermeasure development and also to predict potential future behaviors. We used a structural homology modeling approach to characterize the SARSCoV2 spike protein and predict its binding strength to the human ACE2 receptor. We then explored the possible transmission path by which SARSCoV2 might have crossed to humans by constructing models of ACE2 receptors of relevant species, and calculating the binding energy of SARSCoV2 spike protein to each. Notably, SARSCoV2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated source of the virus. This indicates that SARSCoV2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin , which is most likely explained by a process of convergent evolution. Binding of SARSCoV2 for dog and cat ACE2 was similar to affinity for bat ACE2, all being lower than for humanACE2, and is consistent with only occasional observations of infections of these domestic animals. Overall, the data indicates that SARSCoV2 is uniquely adapted to infect humans, raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere .
The devastating impact of the COVID-19 pandemic caused by SARS coronavirus 2 ( SARS CoV 2 ) has raised important questions about viral origin, mechanisms of zoonotic transfer to humans, whether companion or commercial animals can act as reservoirs for infection, and why there are large variations in SARS-CoV-2 susceptibilities across animal species. Powerful in silico modelling methods can rapidly generate information on newly emerged pathogens to aid countermeasure development and predict future behaviours. Here we report an in silico structural homology modelling, protein-protein docking, and molecular dynamics simulation study of the key infection initiating interaction between the spike protein of SARS-Cov-2 and its target, angiotensin converting enzyme 2 ( ACE2 ) from multiple species. Human ACE2 has the strongest binding interaction, significantly greater than for any species proposed as source of the virus. Binding to pangolin ACE2 was the second strongest, possibly due to the SARS-CoV-2 spike receptor binding domain (RBD) being identical to pangolin CoV spike RDB. Except for snake, pangolin and bat for which permissiveness has not been tested, all those species in the upper half of the affinity range (human, monkey, hamster, dog, ferret) have been shown to be at least moderately permissive to SARS-CoV-2 infection, supporting a correlation between binding affinity and permissiveness. Our data indicates that the earliest isolates of SARS-CoV-2 were surprisingly well adapted to human ACE2, potentially explaining its rapid transmission .
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COVID19
COVID-19
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SARSCoV2
SARS CoV 2
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on the origins of this virus, the mechanisms of any zoonotic transfer from exotic animals
about viral origin, mechanisms of zoonotic transfer
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animals or those used for commercial purposes
or commercial animals
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the reasons for the
why there are
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SARS-CoV-2
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Traditional lab-based methods will ultimately answer many of these questions but take considerable time. In silico modeling methods provide the opportunity to
Powerful in silico modelling methods can
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also to predict potential future behaviors. We used a structural homology modeling approach to characterize the SARSCoV2 spike protein and predict its binding strength to the human
predict future behaviours. Here we report an in silico structural homology modelling, protein-protein docking, and molecular dynamics simulation study of the key infection initiating interaction between the spike protein of SARS-Cov-2 and its target, angiotensin converting enzyme 2 (
R
receptor. We then explored the possible transmission path by which SARSCoV2 might have crossed to humans by constructing models of
) from multiple species. Human
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receptors of relevant species, and calculating the binding energy of SARSCoV2 spike protein to each. Notably, SARSCoV2 spike protein had the highest overall binding energy for human ACE2, greater than all the other tested species including bat, the postulated
has the strongest binding interaction, significantly greater than for any species proposed as
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This indicates that SARSCoV2 is a highly adapted human pathogen. Of the species studied, the next highest binding affinity after human was pangolin , which is most likely explained by a process of convergent evolution. Binding of SARSCoV2 for dog and cat
Binding to pangolin
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was similar to affinity for bat ACE2, all being lower than for humanACE2, and is consistent with only occasional observations of infections of these domestic animals. Overall, the
was the second strongest, possibly due to the SARS-CoV-2 spike receptor binding domain (RBD) being identical to pangolin CoV spike RDB. Except for snake, pangolin and bat for which permissiveness has not been tested, all those species in the upper half of the affinity range (human, monkey, hamster, dog, ferret) have been shown to be at least moderately permissive to SARS-CoV-2 infection, supporting a correlation between binding affinity and permissiveness. Our
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SARSCoV2 is uniquely adapted to infect humans, raising questions as to whether it arose in nature by a rare chance event or whether its origins lie elsewhere
the earliest isolates of SARS-CoV-2 were surprisingly well adapted to human ACE2, potentially explaining its rapid transmission