Structural Variations in Human ACE2 may Influence its Binding with SARS-CoV-2 Spike Protein

Journal of Medical Virology
Mushtaq HussainBasma Aziz


The recent pandemic of COVID-19, caused by SARS-CoV-2, is unarguably the most fearsome compared to the earlier outbreaks caused by other coronaviruses, SARS-CoV and MERS-CoV. Human ACE2 is now established as a receptor for the SARS-CoV-2 spike protein. Where variations in the viral spike protein in turn lead to the cross species transmission of the virus, genetic variations in the host receptor ACE2, may also contribute to the susceptibility and/or resistance against the viral infection. This study aims to explore the binding of the proteins encoded by different human ACE2 allelic variants with SARS-CoV-2 spike protein. Briefly, coding variants of ACE2 corresponding to the reported binding sites for its attachment with coronavirus spike protein were selected and molecular models of these variants were constructed by homology modelling. The models were then superimposed over the native ACE2 and ACE2-spike protein complex, to observe structural changes in the ACE2 variants and their intermolecular interactions with SARS-CoV-2 spike protein respectively. Despite strong overall structural similarities, spatial orientation of the key interacting residues varies in the ACE2 variants compared to the wild type molecule. Most ACE2 varia...Continue Reading


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