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The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

ABSTRACT: The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency, and no approved therapeutics or vaccines are currently available. The viral spike protein S binds membrane-tethered ACE2 on host cells in the lungs to initiate molecular events that ultimately release the viral genome intracellularly. The extracellular protease domain of ACE2 inhibits cell entry of both SARS and SARS-2 coronaviruses by acting as a soluble decoy for receptor binding sites on S, and is a promising candidate for therapeutic and prophylactic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S at a cell surface. Mutations are found across the protein-protein interface and also at buried sites where they are predicted to enhance folding and presentation of the interaction epitope. The mutational landscape offers a preliminary blueprint for engineering high affinity ACE2 receptors to meet this unprecedented challenge.

ORGANISM(S): Homo sapiens

PROVIDER: GSE147194 | GEO | 2020/03/19

REPOSITORIES: GEO

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