Cargando…

Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?

[Image: see text] The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 conf...

Descripción completa

Detalles Bibliográficos
Autores principales: Nguyen, Hoang Linh, Lan, Pham Dang, Thai, Nguyen Quoc, Nissley, Daniel A., O’Brien, Edward P., Li, Mai Suan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433338/
https://www.ncbi.nlm.nih.gov/pubmed/32790406
http://dx.doi.org/10.1021/acs.jpcb.0c04511
_version_ 1783571985859608576
author Nguyen, Hoang Linh
Lan, Pham Dang
Thai, Nguyen Quoc
Nissley, Daniel A.
O’Brien, Edward P.
Li, Mai Suan
author_facet Nguyen, Hoang Linh
Lan, Pham Dang
Thai, Nguyen Quoc
Nissley, Daniel A.
O’Brien, Edward P.
Li, Mai Suan
author_sort Nguyen, Hoang Linh
collection PubMed
description [Image: see text] The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science2020, 367, 1260–1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell2020, 181, 281–292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechnism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions.
format Online
Article
Text
id pubmed-7433338
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-74333382020-08-18 Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV? Nguyen, Hoang Linh Lan, Pham Dang Thai, Nguyen Quoc Nissley, Daniel A. O’Brien, Edward P. Li, Mai Suan J Phys Chem B [Image: see text] The 2019 novel coronavirus (SARS-CoV-2) epidemic, which was first reported in December 2019 in Wuhan, China, was declared a pandemic by the World Health Organization in March 2020. Genetically, SARS-CoV-2 is closely related to SARS-CoV, which caused a global epidemic with 8096 confirmed cases in more than 25 countries from 2002 to 2003. Given the significant morbidity and mortality rate, the current pandemic poses a danger to all of humanity, prompting us to understand the activity of SARS-CoV-2 at the atomic level. Experimental studies have revealed that spike proteins of both SARS-CoV-2 and SARS-CoV bind to angiotensin-converting enzyme 2 (ACE2) before entering the cell for replication. However, the binding affinities reported by different groups seem to contradict each other. Wrapp et al. (Science2020, 367, 1260–1263) showed that the spike protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) more strongly than does SARS-CoV, and this fact may be associated with a greater severity of the new virus. However, Walls et al. (Cell2020, 181, 281–292) reported that SARS-CoV-2 exhibits a higher binding affinity, but the difference between the two variants is relatively small. To understand the binding mechnism and experimental results, we investigated how the receptor binding domain (RBD) of SARS-CoV (SARS-CoV-RBD) and SARS-CoV-2 (SARS-CoV-2-RBD) interacts with a human ACE2-PD using molecular modeling. We applied a coarse-grained model to calculate the dissociation constant and found that SARS-CoV-2 displays a 2-fold higher binding affinity. Using steered all-atom molecular dynamics simulations, we demonstrate that, like a coarse-grained simulation, SARS-CoV-2-RBD was associated with ACE2-PD more strongly than was SARS-CoV-RBD, as evidenced by a higher rupture force and larger pulling work. We show that the binding affinity of both viruses to ACE2 is driven by electrostatic interactions. American Chemical Society 2020-07-29 2020-08-27 /pmc/articles/PMC7433338/ /pubmed/32790406 http://dx.doi.org/10.1021/acs.jpcb.0c04511 Text en Copyright © 2020 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
spellingShingle Nguyen, Hoang Linh
Lan, Pham Dang
Thai, Nguyen Quoc
Nissley, Daniel A.
O’Brien, Edward P.
Li, Mai Suan
Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title_full Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title_fullStr Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title_full_unstemmed Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title_short Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?
title_sort does sars-cov-2 bind to human ace2 more strongly than does sars-cov?
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433338/
https://www.ncbi.nlm.nih.gov/pubmed/32790406
http://dx.doi.org/10.1021/acs.jpcb.0c04511
work_keys_str_mv AT nguyenhoanglinh doessarscov2bindtohumanace2morestronglythandoessarscov
AT lanphamdang doessarscov2bindtohumanace2morestronglythandoessarscov
AT thainguyenquoc doessarscov2bindtohumanace2morestronglythandoessarscov
AT nissleydaniela doessarscov2bindtohumanace2morestronglythandoessarscov
AT obrienedwardp doessarscov2bindtohumanace2morestronglythandoessarscov
AT limaisuan doessarscov2bindtohumanace2morestronglythandoessarscov