<i>In Silico</i> Analysis of High‐Risk Missense Variants in Human <i>ACE2</i> Gene and Susceptibility to SARS‐CoV‐2 Infection
Asmae Saih, Hanâ Baba, Meryem Bouqdayr, Hassan Ghazal, Salsabil Hamdi, Anass Kettani, Lahcen Wakrim
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.