Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.

SARS-CoV-2 virus, the causative agent of Covid-19, has fired up a global pandemic. The virus interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) for an invasion via receptor binding domain (RBD) on its spike protein. To provide a deeper understanding of this interaction, we perf...

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Autores principales:	Van A Ngo, Ramesh K Jha
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8c4421723d7746ec949a8c754bab4410
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spelling	oai:doaj.org-article:8c4421723d7746ec949a8c754bab44102021-12-02T20:04:40ZIdentifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.1932-620310.1371/journal.pone.0257905https://doaj.org/article/8c4421723d7746ec949a8c754bab44102021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257905https://doaj.org/toc/1932-6203SARS-CoV-2 virus, the causative agent of Covid-19, has fired up a global pandemic. The virus interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) for an invasion via receptor binding domain (RBD) on its spike protein. To provide a deeper understanding of this interaction, we performed microsecond simulations of the RBD-ACE2 complex for SARS-CoV-2 and compared it with the closely related SARS-CoV discovered in 2003. We show residues in the RBD of SARS-CoV-2 that were mutated from SARS-CoV, collectively help make the RBD anchor much stronger to the N-terminal part of ACE2 than the corresponding residues on RBD of SARS-CoV. This would result in a reduced dissociation rate of SARS-CoV-2 from human receptor protein compared to SARS-CoV. The phenomenon was consistently observed in simulations beyond 500 ns and was reproducible across different force fields. Altogether, our study adds more insight into the critical dynamics of the key residues at the virus spike and human receptor binding interface and potentially aids the development of diagnostics and therapeutics to combat the pandemic efficiently.Van A NgoRamesh K JhaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0257905 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Van A Ngo Ramesh K Jha Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
description	SARS-CoV-2 virus, the causative agent of Covid-19, has fired up a global pandemic. The virus interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) for an invasion via receptor binding domain (RBD) on its spike protein. To provide a deeper understanding of this interaction, we performed microsecond simulations of the RBD-ACE2 complex for SARS-CoV-2 and compared it with the closely related SARS-CoV discovered in 2003. We show residues in the RBD of SARS-CoV-2 that were mutated from SARS-CoV, collectively help make the RBD anchor much stronger to the N-terminal part of ACE2 than the corresponding residues on RBD of SARS-CoV. This would result in a reduced dissociation rate of SARS-CoV-2 from human receptor protein compared to SARS-CoV. The phenomenon was consistently observed in simulations beyond 500 ns and was reproducible across different force fields. Altogether, our study adds more insight into the critical dynamics of the key residues at the virus spike and human receptor binding interface and potentially aids the development of diagnostics and therapeutics to combat the pandemic efficiently.
format	article
author	Van A Ngo Ramesh K Jha
author_facet	Van A Ngo Ramesh K Jha
author_sort	Van A Ngo
title	Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
title_short	Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
title_full	Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
title_fullStr	Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
title_full_unstemmed	Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.
title_sort	identifying key determinants and dynamics of sars-cov-2/ace2 tight interaction.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/8c4421723d7746ec949a8c754bab4410
work_keys_str_mv	AT vanango identifyingkeydeterminantsanddynamicsofsarscov2ace2tightinteraction AT rameshkjha identifyingkeydeterminantsanddynamicsofsarscov2ace2tightinteraction
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Identifying key determinants and dynamics of SARS-CoV-2/ACE2 tight interaction.

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