Abstract
We herein report a computational study on the implications of SARS-CoV-2 RBD mutations and the Angiotensin Converting Enzyme 2 (ACE2) receptor genetic variations on the stability of the virus-host association. In silico analysis of the complex between the virus’ mutated forms and ACE2 isoform 1 showed that out of 351 RBD point mutations, 83% destabilizes the complex, while 17% have mild stabilizing effect. Study of the complex SARS-CoV-2 Wuhan strain RBD region /ACE2 isoform 1, 6LZG PDB 3D model revealed 18 contact residues. Interestingly, mutations occurring in 15 out of these residues show variations in the patterns of polar and hydrophobic interactions as compared to the original complex. Similarly, comparison of the effect on the complex stability of different ACE2 variants showed that the pattern of molecular interactions and the virus-receptor complex stability varies also according to ACE2 polymorphism. This could explain the large inter-individual variation of disease susceptibility and/or severity. The observation of a high variability in the interactions patterns highlights the complexity of the molecular interplay between SARS-CoV-2 and the ACE2 receptor. We infer that it is important to consider both ACE2 genetic variants and SARS-CoV-2 RBD mutations to assess the stability of the virus-receptor association and evaluate the infectivity of circulating SARS-CoV-2. These findings point toward the importance of individuals genetic typing of the circulating viral form as well as the ACE2 receptor. This will offer a good molecular ground to adjust the mitigation efforts for a better control of the virus spreading.
Competing Interest Statement
The authors have declared no competing interest.
