In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin

Abstract 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...

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Autores principales:	Sakshi Piplani, Puneet Kumar Singh, David A. Winkler, Nikolai Petrovsky
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/06be79b51fc445ad8d4bec52fd1e44cb
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spelling	oai:doaj.org-article:06be79b51fc445ad8d4bec52fd1e44cb2021-12-02T17:14:29ZIn silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin10.1038/s41598-021-92388-52045-2322https://doaj.org/article/06be79b51fc445ad8d4bec52fd1e44cb2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92388-5https://doaj.org/toc/2045-2322Abstract 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.Sakshi PiplaniPuneet Kumar SinghDavid A. WinklerNikolai PetrovskyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sakshi Piplani Puneet Kumar Singh David A. Winkler Nikolai Petrovsky In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
description	Abstract 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.
format	article
author	Sakshi Piplani Puneet Kumar Singh David A. Winkler Nikolai Petrovsky
author_facet	Sakshi Piplani Puneet Kumar Singh David A. Winkler Nikolai Petrovsky
author_sort	Sakshi Piplani
title	In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
title_short	In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
title_full	In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
title_fullStr	In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
title_full_unstemmed	In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin
title_sort	in silico comparison of sars-cov-2 spike protein-ace2 binding affinities across species and implications for virus origin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/06be79b51fc445ad8d4bec52fd1e44cb
work_keys_str_mv	AT sakshipiplani insilicocomparisonofsarscov2spikeproteinace2bindingaffinitiesacrossspeciesandimplicationsforvirusorigin AT puneetkumarsingh insilicocomparisonofsarscov2spikeproteinace2bindingaffinitiesacrossspeciesandimplicationsforvirusorigin AT davidawinkler insilicocomparisonofsarscov2spikeproteinace2bindingaffinitiesacrossspeciesandimplicationsforvirusorigin AT nikolaipetrovsky insilicocomparisonofsarscov2spikeproteinace2bindingaffinitiesacrossspeciesandimplicationsforvirusorigin
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In silico comparison of SARS-CoV-2 spike protein-ACE2 binding affinities across species and implications for virus origin

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