  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.
