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In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection

SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various...

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Autores principales: Saih, Asmae, Baba, Hana, Bouqdayr, Meryem, Ghazal, Hassan, Hamdi, Salsabil, Kettani, Anass, Wakrim, Lahcen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040925/
https://www.ncbi.nlm.nih.gov/pubmed/33884270
http://dx.doi.org/10.1155/2021/6685840
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author Saih, Asmae
Baba, Hana
Bouqdayr, Meryem
Ghazal, Hassan
Hamdi, Salsabil
Kettani, Anass
Wakrim, Lahcen
author_facet Saih, Asmae
Baba, Hana
Bouqdayr, Meryem
Ghazal, Hassan
Hamdi, Salsabil
Kettani, Anass
Wakrim, Lahcen
author_sort Saih, Asmae
collection PubMed
description SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various bioinformatics tools were used including SIFT, PANTHER, PROVEAN, PolyPhen2.0, I. Mutant Suite, MUpro, SWISS-MODEL, Project HOPE, ModPred, QMEAN, ConSurf, and STRING. All twelve ACE2 nsSNPs were analyzed. Six ACE2 high-risk pathogenic nsSNPs (D427Y, R514G, R708W, R710C, R716C, and R768W) were found to be the most damaging by at least six software tools (cumulative score between 6 and 7) and exert deleterious effect on the ACE2 protein structure and likely function. Additionally, they revealed high conservation, less stability, and having a role in posttranslation modifications such a proteolytic cleavage or ADP-ribosylation. This in silico analysis provides information about functional nucleotide variants that have an impact on the ACE2 protein structure and function and therefore susceptibility to SARS-CoV-2.
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spelling pubmed-80409252021-04-20 In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection Saih, Asmae Baba, Hana Bouqdayr, Meryem Ghazal, Hassan Hamdi, Salsabil Kettani, Anass Wakrim, Lahcen Biomed Res Int Research Article SARS-CoV-2 coronavirus uses for entry to human host cells a SARS-CoV receptor of the angiotensin-converting enzyme (ACE2) that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of ACE2 missense variants on protein structure, stability, and function, various bioinformatics tools were used including SIFT, PANTHER, PROVEAN, PolyPhen2.0, I. Mutant Suite, MUpro, SWISS-MODEL, Project HOPE, ModPred, QMEAN, ConSurf, and STRING. All twelve ACE2 nsSNPs were analyzed. Six ACE2 high-risk pathogenic nsSNPs (D427Y, R514G, R708W, R710C, R716C, and R768W) were found to be the most damaging by at least six software tools (cumulative score between 6 and 7) and exert deleterious effect on the ACE2 protein structure and likely function. Additionally, they revealed high conservation, less stability, and having a role in posttranslation modifications such a proteolytic cleavage or ADP-ribosylation. This in silico analysis provides information about functional nucleotide variants that have an impact on the ACE2 protein structure and function and therefore susceptibility to SARS-CoV-2. Hindawi 2021-04-09 /pmc/articles/PMC8040925/ /pubmed/33884270 http://dx.doi.org/10.1155/2021/6685840 Text en Copyright © 2021 Asmae Saih et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Saih, Asmae
Baba, Hana
Bouqdayr, Meryem
Ghazal, Hassan
Hamdi, Salsabil
Kettani, Anass
Wakrim, Lahcen
In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title_full In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title_fullStr In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title_full_unstemmed In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title_short In Silico Analysis of High-Risk Missense Variants in Human ACE2 Gene and Susceptibility to SARS-CoV-2 Infection
title_sort in silico analysis of high-risk missense variants in human ace2 gene and susceptibility to sars-cov-2 infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040925/
https://www.ncbi.nlm.nih.gov/pubmed/33884270
http://dx.doi.org/10.1155/2021/6685840
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