Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations

SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane...

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Autores principales:	Damiano Buratto, Abhishek Saxena, Qun Ji, Guang Yang, Sergio Pantano, Francesco Zonta
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	COVID-19 SARS-CoV-2 Spike-RBD human ACE2 binding affinity neutralizing antibodies Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/af8050795abc45a8b32ffeecb46773d2
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spelling	oai:doaj.org-article:af8050795abc45a8b32ffeecb46773d22021-11-11T08:48:53ZRapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations1664-322410.3389/fimmu.2021.730099https://doaj.org/article/af8050795abc45a8b32ffeecb46773d22021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.730099/fullhttps://doaj.org/toc/1664-3224SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane for entry. The spike glycoprotein of circulating SARS-CoV-2 genomes is a mutation hotspot. Some mutations may affect the binding affinity for hACE2, while others may modulate S-glycoprotein expression, or they could result in a virus that can escape from antibodies generated by infection with the original variant or by vaccination. Since a large number of variants are emerging, it is of vital importance to be able to rapidly assess their characteristics: while changes of binding affinity alone do not always cause direct advantages for the virus, they still can provide important insights on where the evolutionary pressure is directed. Here, we propose a simple and cost-effective computational protocol based on Molecular Dynamics simulations to rapidly screen the ability of mutated spike protein to bind to the hACE2 receptor and selected neutralizing biomolecules. Our results show that it is possible to achieve rapid and reliable predictions of binding affinities. A similar approach can be used to perform preliminary screenings of the potential effects of S-RBD mutations, helping to prioritize the more time-consuming and expensive experimental work.Damiano BurattoAbhishek SaxenaQun JiGuang YangSergio PantanoSergio PantanoFrancesco ZontaFrontiers Media S.A.articleCOVID-19SARS-CoV-2Spike-RBDhuman ACE2binding affinityneutralizing antibodiesImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 SARS-CoV-2 Spike-RBD human ACE2 binding affinity neutralizing antibodies Immunologic diseases. Allergy RC581-607
spellingShingle	COVID-19 SARS-CoV-2 Spike-RBD human ACE2 binding affinity neutralizing antibodies Immunologic diseases. Allergy RC581-607 Damiano Buratto Abhishek Saxena Qun Ji Guang Yang Sergio Pantano Sergio Pantano Francesco Zonta Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
description	SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane for entry. The spike glycoprotein of circulating SARS-CoV-2 genomes is a mutation hotspot. Some mutations may affect the binding affinity for hACE2, while others may modulate S-glycoprotein expression, or they could result in a virus that can escape from antibodies generated by infection with the original variant or by vaccination. Since a large number of variants are emerging, it is of vital importance to be able to rapidly assess their characteristics: while changes of binding affinity alone do not always cause direct advantages for the virus, they still can provide important insights on where the evolutionary pressure is directed. Here, we propose a simple and cost-effective computational protocol based on Molecular Dynamics simulations to rapidly screen the ability of mutated spike protein to bind to the hACE2 receptor and selected neutralizing biomolecules. Our results show that it is possible to achieve rapid and reliable predictions of binding affinities. A similar approach can be used to perform preliminary screenings of the potential effects of S-RBD mutations, helping to prioritize the more time-consuming and expensive experimental work.
format	article
author	Damiano Buratto Abhishek Saxena Qun Ji Guang Yang Sergio Pantano Sergio Pantano Francesco Zonta
author_facet	Damiano Buratto Abhishek Saxena Qun Ji Guang Yang Sergio Pantano Sergio Pantano Francesco Zonta
author_sort	Damiano Buratto
title	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
title_short	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
title_full	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
title_fullStr	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
title_full_unstemmed	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
title_sort	rapid assessment of binding affinity of sars-cov-2 spike protein to the human angiotensin-converting enzyme 2 receptor and to neutralizing biomolecules based on computer simulations
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/af8050795abc45a8b32ffeecb46773d2
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Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations

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