While mutations are often associated with causing diseases such as cancer, Xingyi Guo, PhD, and colleagues have discovered genetic alterations that might reduce infectivity by SARS-CoV-2, the virus that causes COVID-19.
Their work details genetic variations in the ACE2 cell surface receptor that binds to the viral spike (S) protein, how these mutations might destabilize the receptor, and which populations are most likely to carry mutant forms of the receptor.
Using a database containing over 100,000 individuals’ DNA sequences, the researchers identified and characterized 12 validated alterations within ACE2 that are a result of a one nucleotide change within the genetic code.
These variants were computationally modeled to determine their contribution to destabilizing the receptor and reducing its activity. One mutation implicated in altered receptor structure was present only in Asian populations.
The paper, published in the Journal of Translational Medicine, gives genetic context for potential differences in SARS-CoV-2 infectivity and suggests possible new strategies for identifying susceptible populations.