Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein

• Published in: PloS one Vol. 16; no. 5; p. e0251585
• Main Authors: Heinzelman, Pete, Romero, Philip A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.05.2021; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Angiotensin converting enzyme; Biology and Life Sciences; Medicine and health sciences; Physical Sciences; Proteins; Research and Analysis Methods; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0251585

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.