posted on 2021-06-30, 01:50authored bySakshi Piplani, Puneet Singh, David WinklerDavid Winkler, Nikolai Petrovsky
The
devastating impact of the COVID-19 pandemic caused by SARS–coronavirus 2
(SARS-CoV-2) has raised important questions about its origins and the mechanism
of its transfer to humans. A further question was whether companion or
commercial animals could act as SARS-CoV-2 vectors, with early data suggesting
susceptibility is species specific. To better understand SARS-CoV-2 species
susceptibility, we undertook an in silico structural homology modelling, protein–protein
docking, and molecular dynamics simulation study of SARS-CoV-2 spike protein’s
ability to bind angiotensin converting enzyme 2 (ACE2) from relevant species.
Spike protein exhibited the highest binding to human (h)ACE2 of all the species
tested, forming the highest number of hydrogen bonds with hACE2. Interestingly,
pangolin ACE2 showed the next highest binding affinity despite having a
relatively low sequence homology, whereas the affinity of monkey ACE2 was much
lower despite its high sequence similarity to hACE2. These differences
highlight the power of a structural versus a sequence-based approach to
cross-species analyses. ACE2 species in the upper half of the predicted
affinity range (monkey, hamster, dog, ferret, cat) have been shown to be
permissive to SARS-CoV-2 infection, supporting a correlation between binding
affinity and infection susceptibility. These findings show that the earliest
known SARS-CoV-2 isolates were surprisingly well adapted to bind strongly to
human ACE2, helping explain its efficient human to human respiratory
transmission. This study highlights how in silico structural modelling methods
can be used to rapidly generate information on novel viruses to help predict
their behaviour and aid in countermeasure development.
History
Publication Date
2021-06-24
Journal
Scientific Reports
Volume
11
Article Number
13063
Pagination
13p.
Publisher
Springer Nature
ISSN
2045-2322
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