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

被引:11
作者
Saih, Asmae [1 ,2 ]
Baba, Hana [1 ,2 ]
Bouqdayr, Meryem [1 ,2 ]
Ghazal, Hassan [3 ,4 ]
Hamdi, Salsabil [5 ]
Kettani, Anass [2 ]
Wakrim, Lahcen [1 ]
机构
[1] Inst Pasteur Maroc, Virol Unit, Immunovirol Lab, Casablanca 20360, Morocco
[2] Hassan II Univ Casablanca, Lab Biol & Hlth, Fac Sci Ben MSik, URAC 34, Casablanca, Morocco
[3] Natl Ctr Sci Tech Res CNRST, Rabat 10102, Morocco
[4] Mohammed VI Univ Hlth Sci, Dept Fundamental Sci, Sch Med, Casablanca, Morocco
[5] Inst Pasteur Maroc, Environm Hlth Lab, Casablanca 20360, Morocco
关键词
ANGIOTENSIN-CONVERTING ENZYME-2; STABILITY CHANGES; PROTEIN; POLYMORPHISMS; COVID-19; SEQUENCE; INSIGHTS; QUALITY; TMPRSS2; SERVER;
D O I
10.1155/2021/6685840
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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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页数:10
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