Bi-paratopic and multivalent VH domains block ACE2 binding and neutralize SARS-CoV-2

• Published in: Nature chemical biology Vol. 17; no. 1; pp. 113 - 121
• Main Authors: Bracken, Colton J., Lim, Shion A., Solomon, Paige, Rettko, Nicholas J., Nguyen, Duy P., Zha, Beth Shoshana, Schaefer, Kaitlin, Byrnes, James R., Zhou, Jie, Lui, Irene, Liu, Jia, Pance, Katarina, Zhou, Xin X., Leung, Kevin K., Wells, James A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2021; Nature Publishing Group
• Subjects: 631/154/51; 631/250/255; 631/326/596/4130; 631/45/535; 631/92/469; ACE2; Affinity; Angiotensin; Angiotensin-converting enzyme 2; Angiotensin-Converting Enzyme 2 - antagonists & inhibitors; Angiotensin-Converting Enzyme 2 - chemistry; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - immunology; Animals; Antibodies; Antibodies, Neutralizing - chemistry; Antibodies, Neutralizing - genetics; Antibodies, Neutralizing - immunology; Antibodies, Viral - chemistry; Antibodies, Viral - genetics; Antibodies, Viral - immunology; Binders; Binding sites; Binding Sites, Antibody - genetics; Binding Sites, Antibody - immunology; Biochemical Engineering; Biochemistry; Bioorganic Chemistry; Cell Biology; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Chlorocebus aethiops; COVID-19; Cryoelectron Microscopy; Epitopes; HEK293 Cells; Humans; Models, Molecular; Neutralization; Neutralizing; Peptide Library; Peptidyl-dipeptidase A; Phages; Prophylaxis; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Receptors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Single-Chain Antibodies - chemistry; Single-Chain Antibodies - genetics; Single-Chain Antibodies - immunology; Spike Glycoprotein, Coronavirus - antagonists & inhibitors; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - genetics; Spike Glycoprotein, Coronavirus - immunology; Spike protein; Vero Cells

Neutralizing agents against SARS-CoV-2 are urgently needed for the treatment and prophylaxis of COVID-19. Here, we present a strategy to rapidly identify and assemble synthetic human variable heavy (VH) domains toward neutralizing epitopes. We constructed a VH-phage library and targeted the angioten...