Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant ( K D ) of 0.99–35.5 nM. The monomeric sdAbs show half maximal neutralization concentration (EC 50 ) of 0.0009–0.07 µg/mL and 0.13–0.51 µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies. Here, using a humanized phage display library with recombinant SARS- CoV-2 receptor binding domain (RBD) proteins, the authors identify a number of single domain antibodies (sdAbs) that neutralize SARS-CoV-2 in vitro by inhibiting the interaction of the RDB with the host entry receptor ACE2.
【저자키워드】 SARS-CoV-2, Antibody fragment therapy, 【초록키워드】 viral infection, ACE2, coronavirus, antibody, neutralization, Proteins, in vitro, viral entry, Receptor binding domain, Spread, RBD, SARS- CoV-2, Neutralizing, experiment, fusion, Therapies, binding kinetics, SARS-CoV-2 spike, association, Interaction, Concentration, SARS-CoV-2 RBD, antiviral therapies, Support, acute respiratory syndrome, domain, neutralization activity, entry receptor, blockade, receptor ACE2, Host, humanized, neutralize, human IgG1 Fc, IMPROVE, identify, significantly, inhibit, generate, inhibiting, monomeric, 【제목키워드】 antibody, Receptor binding domain, domain, neutralize,