Engineered ACE2 receptor therapy overcomes mutational escape of SARS-CoV-2

• Published in: Nature communications Vol. 12; no. 1; pp. 3802 - 13
• Main Authors: Higuchi, Yusuke, Suzuki, Tatsuya, Arimori, Takao, Ikemura, Nariko, Mihara, Emiko, Kirita, Yuhei, Ohgitani, Eriko, Mazda, Osam, Motooka, Daisuke, Nakamura, Shota, Sakai, Yusuke, Itoh, Yumi, Sugihara, Fuminori, Matsuura, Yoshiharu, Matoba, Satoaki, Okamoto, Toru, Takagi, Junichi, Hoshino, Atsushi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 21.06.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 42/70; 49/31; 631/154/51/1568; 631/326/596/4130; 82/1; 82/103; 82/47; 82/80; 82/83; ACE2; Affinity; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - metabolism; Angiotensin-Converting Enzyme 2 - pharmacology; Animals; Binding; Cells, Cultured; Conformation; COVID-19; COVID-19 - metabolism; COVID-19 - virology; COVID-19 Drug Treatment; Cricetinae; Crystallography, X-Ray; Disease Models, Animal; Hamsters; Humanities and Social Sciences; Humans; Hydrogen bonding; Hydrophobicity; Male; Molecular Dynamics Simulation; multidisciplinary; Mutagenesis; Mutation; Pandemics; Protein Binding; Protein Engineering - methods; Random mutagenesis; Receptors; SARS-CoV-2 - drug effects; SARS-CoV-2 - isolation & purification; SARS-CoV-2 - metabolism; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - metabolism; Structural stability; Therapeutic applications; Viral diseases; Viruses

SARS-CoV-2 has mutated during the global pandemic leading to viral adaptation to medications and vaccinations. Here we describe an engineered human virus receptor, ACE2, by mutagenesis and screening for binding to the receptor binding domain (RBD). Three cycles of random mutagenesis and cell sorting...