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

ABSTRACT: Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can have a major impact in leveraging 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 can have a strong influence upon the ACE2-spike interaction. These findings illuminate new links between ACE2 sequence and spike recognition, and will find wide-ranging utility in SARS-CoV-2 fundamental research, epidemiological analyses, and clinical trial design.

SUBMITTER: Heinzelman P

PROVIDER: S-EPMC7523126 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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

Heinzelman Pete P Romero Philip A PA

bioRxiv : the preprint server for biology 20200917

Understanding how human ACE2 genetic variants differ in their recognition by SARS-CoV-2 can have a major impact in leveraging 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 can have a strong influence upon t ...[more]

PMID: 32995796

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