Humanized Single Domain Antibodies Neutralize SARS-CoV-2 by Targeting Spike Receptor Binding Domain

Xiaojing Chi, Xiuying Liu, Conghui Wang, Xinhui Zhang, Lili Ren, Qi Jin, Jianwei Wang, Wei Yang

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Received Date: 29th March 20


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread across more than 180 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 and elimination 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 neutralization IC50 value of 0.003∼0.3 µg/mL in pseudotyped particle entry assay, and 0.23∼0.50 µg/mL in authentic SARS-CoV-2 infection assay. Competitive ligand-binding data suggested that the sdAbs 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.


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