Analysis of High-Risk Missense Variants in Human 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 () that catalyzes the conversion of angiotensin II into angiotensin (1-7). To understand the effect of 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 nsSNPs were analyzed. Six 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 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 analysis provides information about functional nucleotide variants that have an impact on the protein structure and function and therefore susceptibility to SARS-CoV-2.