RT Journal Article
SR Electronic
T1 Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.04.14.042010
DO 10.1101/2020.04.14.042010
A1 Xiaojing Chi
A1 Xiuying Liu
A1 Conghui Wang
A1 Xinhui Zhang
A1 Lili Ren
A1 Qi Jin
A1 Jianwei Wang
A1 Wei Yang
YR 2020
UL http://biorxiv.org/content/early/2020/04/15/2020.04.14.042010.abstract
AB Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across more than 200 countries and regions, leading to an unprecedented medical burden and live lost. SARS-CoV-2 specific antivirals or prophylactic vaccines are not available. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Using SARS-CoV-2 spike RBD as a bait, we have discovered a panel of humanized single domain antibodies (sdAbs). These sdAbs revealed binding kinetics with the equilibrium dissociation constant (KD) of 0.7~33 nM. The monomeric sdAbs showed half maximal inhibitory concentration (IC50) of 0.003~0.3 μg/mL in pseudotyped particle neutralization assay, and 0.23~0.50 μg/mL in authentic SARS-CoV-2 neutralization assay. Competitive ligand-binding data suggested that the sdAbs either completely blocked or significantly inhibited the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Finally, we showed that fusion of the human IgG1 Fc to sdAbs improved their neutralization activity by tens of times. These results reveal the novel SARS-CoV-2 RBD targeting sdAbs and pave a road for antibody drug development.Competing Interest StatementThe authors have declared no competing interest.