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.
【초록키워드】 SARS-CoV-2, ACE2, coronavirus, SARS-CoV, susceptibility, bioinformatics, variant, SARS-CoV-2 coronavirus, Protein, stability, protein structure, receptor, in silico analysis, information, Angiotensin-converting enzyme, Angiotensin II, nucleotide, angiotensin, ACE2 protein, Deleterious, host cells, pathogenic, cumulative score, STRING, conversion, Modification, missense variant, ADP-ribosylation, ConSurf, proteolytic cleavage, PROVEAN, SIFT, human host cells, analyzed, functional, provide, were used, less, human host cell, 【제목키워드】 SARS-CoV-2, ACE2, Human,