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

Fedaa Ali1, Menattallah Elserafy2, Mohamed H Alkordi3

  • 1Department of Sciences, University College Groningen, University of Groningen, Hoendiepskade 23/24, 9718, BG Groningen, Netherlands.

Biochemistry and Biophysics Reports
|August 27, 2020
PubMed
Summary

Genetic variations in the ACE2 receptor influence SARS-CoV-2 binding. Some variants, like ACE2-K26R in Ashkenazi Jews, weaken viral attraction, while others increase it, potentially impacting population susceptibility to COVID-19.

Keywords:
ACE2 variantsPopulationsSARS-CoV-2 bindingSingle nucleotide variants

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Area of Science:

  • Genetics
  • Virology
  • Computational Chemistry

Background:

  • Population susceptibility to SARS-CoV-2 infection remains unclear.
  • The angiotensin-converting enzyme 2 (ACE2) receptor is the primary entry point for SARS-CoV-2.
  • Genetic variations in ACE2 may influence viral binding and infection risk.

Purpose of the Study:

  • To investigate the impact of common ACE2 coding variants on SARS-CoV-2 binding.
  • To analyze the distribution of these variants across diverse global populations.

Main Methods:

  • Analysis of ACE2 coding variants in different populations.
  • Computational chemistry calculations to simulate SARS-CoV-2/ACE2 interactions.
  • Assessment of electrostatic attraction changes due to specific variants.

Main Results:

  • ACE2-K26R, prevalent in Ashkenazi Jews, reduces electrostatic attraction between SARS-CoV-2 and ACE2.
  • ACE2-I468V, R219C, K341R, D206G, and G211R variants increase electrostatic attraction, with varying binding strengths.
  • These variants are found in East Asian, South Asian, African, African American, and European populations.

Conclusions:

  • Specific ACE2 variants differentially modulate SARS-CoV-2 binding affinity.
  • Genetic background may contribute to varying population susceptibility to SARS-CoV-2.
  • Further research is needed to correlate these findings with clinical outcomes.