Humanized single domain antibodies neutralize SARS-CoV-2 by targeting the spike receptor binding domain
Fecha
2020Autor
Chi, Xiaojing
Liu, Xiuying
Wang, Conghui
Zhang, Xinhui
Li, Xiang
Hou, Jianhua
Ren, Lili
Jin, Qi
Wang, Jianwei
Yang, Wei
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Resumen
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 (KD) of 0.99–35.5
nM. The monomeric sdAbs show half maximal neutralization concentration (EC50) 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.
Palabras clave
SARS-CoV-2; Domain antibodiesEnlace al recurso
https://doi.org/10.1038/s41467-020-18387-8Colecciones
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