Abstract
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.
Highlights
During December 2019 in Wuhan, China, a novel infectious disease called the coronavirus disease 2019 or COVID-19 was detected and found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
SIFT, PolyPhen 2.0, PROVEAN, and PANTHER algorithms were used to predict the functional effects of mutation on the protein
Angiotensin-converting enzyme 2 (ACE2) plays an important role in the renin-angiotensin aldosterone system by metabolizing angiotensin II to angiotensin (1-7) [11]. This important enzyme was identified as a functional receptor for the severe acute respiratory syndrome coronavirus (SARS-CoV) and the novel coronavirus (SARS-CoV-2) [11]
Summary
During December 2019 in Wuhan, China, a novel infectious disease called the coronavirus disease 2019 or COVID-19 was detected and found to be caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Later on, it was declared as a pandemic by the World Health Organization (WHO) on March 2020 [1, 2]. The ACE2 gene is located on the chromosome X, at the position Xp22. It contains 18 exons that show a striking resemblance in exons size and organization to those of the ACE gene [5, 6]. The complete cDNA sequence of ACE2 encodes an 805 amino acid protein, which is composed mainly of an N-terminal signal peptide (17 amino acid residues), a peptidase domain (positioning from 19-615 amino acids), and a C-terminal collectrin, which plays a significant role as a regulator of renal amino acid transportation, insulin exocytosis, and β-cell proliferation [5, 7]
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