In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a newly-discovered coronavirus and responsible for the spread of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infected millions of people in the world and immediately became a pandemic in March 2020. SARS-CoV-2 belongs to th...

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Autores principales:	Farzaneh Jafary, Sepideh Jafari, Mohamad Reza Ganjalikhany
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2fb603d2d14949b984570c78da92d5f7
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spelling	oai:doaj.org-article:2fb603d2d14949b984570c78da92d5f72021-12-02T17:04:34ZIn silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 210.1038/s41598-021-86380-22045-2322https://doaj.org/article/2fb603d2d14949b984570c78da92d5f72021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86380-2https://doaj.org/toc/2045-2322Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a newly-discovered coronavirus and responsible for the spread of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infected millions of people in the world and immediately became a pandemic in March 2020. SARS-CoV-2 belongs to the beta-coronavirus genus of the large family of Coronaviridae. It is now known that its surface spike glycoprotein binds to the angiotensin-converting enzyme-2 (ACE2), which is expressed on the lung epithelial cells, mediates the fusion of the cellular and viral membranes, and facilitates the entry of viral genome to the host cell. Therefore, blocking the virus-cell interaction could be a potential target for the prevention of viral infection. The binding of SARS-CoV-2 to ACE2 is a protein–protein interaction, and so, analyzing the structure of the spike glycoprotein of SARS-CoV-2 and its underlying mechanism to bind the host cell receptor would be useful for the management and treatment of COVID-19. In this study, we performed comparative in silico studies to deeply understand the structural and functional details of the interaction between the spike glycoprotein of SARS-CoV-2 and its cognate cellular receptor ACE2. According to our results, the affinity of the ACE2 receptor for SARS-CoV-2 was higher than SARS-CoV. According to the free energy decomposition of the spike glycoprotein-ACE2 complex, we found critical points in three areas which are responsible for the increased binding affinity of SARS-CoV-2 compared with SARS-CoV. These mutations occurred at the receptor-binding domain of the spike glycoprotein that play an essential role in the increasing the affinity of coronavirus to ACE2. For instance, mutations Pro462Ala and Leu472Phe resulted in the altered binding energy from − 2 kcal mol−1 in SARS-COV to − 6 kcal mol−1 in SARS-COV-2. The results demonstrated that some mutations in the receptor-binding motif could be considered as a hot-point for designing potential drugs to inhibit the interaction between the spike glycoprotein and ACE2.Farzaneh JafarySepideh JafariMohamad Reza GanjalikhanyNature 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 Farzaneh Jafary Sepideh Jafari Mohamad Reza Ganjalikhany In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
description	Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a newly-discovered coronavirus and responsible for the spread of coronavirus disease 2019 (COVID-19). SARS-CoV-2 infected millions of people in the world and immediately became a pandemic in March 2020. SARS-CoV-2 belongs to the beta-coronavirus genus of the large family of Coronaviridae. It is now known that its surface spike glycoprotein binds to the angiotensin-converting enzyme-2 (ACE2), which is expressed on the lung epithelial cells, mediates the fusion of the cellular and viral membranes, and facilitates the entry of viral genome to the host cell. Therefore, blocking the virus-cell interaction could be a potential target for the prevention of viral infection. The binding of SARS-CoV-2 to ACE2 is a protein–protein interaction, and so, analyzing the structure of the spike glycoprotein of SARS-CoV-2 and its underlying mechanism to bind the host cell receptor would be useful for the management and treatment of COVID-19. In this study, we performed comparative in silico studies to deeply understand the structural and functional details of the interaction between the spike glycoprotein of SARS-CoV-2 and its cognate cellular receptor ACE2. According to our results, the affinity of the ACE2 receptor for SARS-CoV-2 was higher than SARS-CoV. According to the free energy decomposition of the spike glycoprotein-ACE2 complex, we found critical points in three areas which are responsible for the increased binding affinity of SARS-CoV-2 compared with SARS-CoV. These mutations occurred at the receptor-binding domain of the spike glycoprotein that play an essential role in the increasing the affinity of coronavirus to ACE2. For instance, mutations Pro462Ala and Leu472Phe resulted in the altered binding energy from − 2 kcal mol−1 in SARS-COV to − 6 kcal mol−1 in SARS-COV-2. The results demonstrated that some mutations in the receptor-binding motif could be considered as a hot-point for designing potential drugs to inhibit the interaction between the spike glycoprotein and ACE2.
format	article
author	Farzaneh Jafary Sepideh Jafari Mohamad Reza Ganjalikhany
author_facet	Farzaneh Jafary Sepideh Jafari Mohamad Reza Ganjalikhany
author_sort	Farzaneh Jafary
title	In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
title_short	In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
title_full	In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
title_fullStr	In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
title_full_unstemmed	In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2
title_sort	in silico investigation of critical binding pattern in sars-cov-2 spike protein with angiotensin-converting enzyme 2
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2fb603d2d14949b984570c78da92d5f7
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In silico investigation of critical binding pattern in SARS-CoV-2 spike protein with angiotensin-converting enzyme 2

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