ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity

Abstract

The susceptibility of different populations to the SARS-CoV-2 infection is not yet understood. A deeper analysis of the genomes of individuals from different populations might explain their risk for infection. In this study, a combined analysis of ACE2 coding variants in different populations and computational chemistry calculations are conducted in order to probe the potential effects of ACE2 coding variants on SARS-CoV-2/ACE2 binding affinity. Our study reveals novel interaction data on the variants and SARS-CoV-2. We could show that ACE2-K26R; which is more frequent in the Ashkenazi Jewish population decrease the electrostatic attraction between SARS-CoV-2 and ACE2. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R were found to increase the electrostatic attraction and increase the binding to SARS-CoV-2; ordered by the strength of binding from weakest to strongest. I468V, R219C, K341R, D206G and G211R were more frequent in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. SARS-CoV-2/ACE2 interface in the WT protein and corresponding variants is showed to be a dominated by van der Waals (vdW) interactions. All the mutations except K341R induce an increase in the vdW attractions between the ACE2 and the SARS-CoV-2. The largest increase of is observed for the R219C mutant.

Variants in ACE2; potential influences on virus infection and COVID-19 severity

“…Their results showed that two mutations have different frequencies in these two races, affecting ACE2 binding to spike protein. In another study on ACE2 variants in different ethnicities, Lys26Arg mutation in Ashkenazi Jews reduced ACE2 affinity, in contrast to mutations in other populations, including East Asian (Ile468Val), South Asian (Arg219Cys), African and African American (Lys341Arg), European (Asp206Gly), European and South Asian (Gly211Arg) ( Ali et al, 2020 ). In an independent study, ACE2 genotypes in Africa and Eastern Mediterranean population were considered protective against COVID-19 ( Karahalil and Elkama, 2020 ).…”

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

“…In contrast, the virus binds more to missense variants ACE-I468V, R219C, K341R, D206G, and G211R (in increasing order), corresponding to frequencies observed in East Asian, South Asian, African and African American, European, European and South Asian populations, respectively. The latter isoforms exhibit higher electrostatic attraction, dominated by van der Waals forces (Ali et al, 2020 ).…”

“…Through these approaches, host-cell selectivity of viral receptors could be narrowed down to the level of cell populations, and subpopulations within a tissue or organ with great precision, with inherent prophylactic and therapeutic implications. Differences in the expression of ACE2 missense mutants in different ethnicities were reported (Ali et al, 2020 ). Such heterogeneity could also be reflected at the tissue and cell levels in a given individual, explaining the variabilities in risk, susceptibility and vulnerability of certain organs to become targets of the disease.…”

While We Wait for a Vaccine Against SARS-CoV-2, Why Not Think About Available Drugs?

“…In contrast, the virus binds more to missense variants ACE-I468V, R219C, K341R, D206G, and G211R (in increasing order), corresponding to frequencies observed in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. The latter isoforms exhibit higher electrostatic attraction, dominated by van der Waals forces (Ali et al 2020).…”

“…Through these approaches, host-cell selectivity of viral receptors could be narrowed down to the level of cell populations, and subpopulations within a tissue or organ with great precision, with inherent prophylactic and therapeutic implications. Differences in the expression of ACE2 missense mutants in different ethnicities were reported (Ali et al 2020). Such heterogeneity could also be reflected at the tissue and cell levels in a given individual, explaining the variabilities in risk, susceptibility and vulnerability of certain organs to become targets of the disease.…”