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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.
Acceso Abierto
Atribución-NoComercial-SinDerivadas
10.1101/2020.04.14.042010
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 ug/mL in pseudotyped particle neutralization assay, and 0.23-0.50 ug/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.
www.biorxiv.org
2020
Artículo
https://www.biorxiv.org/content/10.1101/2020.04.14.042010v1.full.pdf
Inglés
VIRUS RESPIRATORIOS
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