Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can facilitate the leveraging of ACE2 as an axis for treating and preventing COVID-19. In this work, we experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and could find substantial utility in further fundamental research that augments epidemiological analyses and clinical trial design in the contexts of both existing strains of SARS-CoV-2 and novel variants that may arise in the future.
【초록키워드】 COVID-19, SARS-CoV-2, ACE2, variant, virus, human ACE2, Clinical trial design, Research, understanding, epidemiological, Genetic variant, mutant, utility, Interaction, Analysis, strain, complementary, Recognition, SNVs, axis, ACE2 residues, ACE2 sequence, identify, facilitate, ACE2 residue, single-nucleotide, 【제목키워드】 variant, Spike protein, human ACE2, the SARS-CoV-2,