Data_Sheet_1_Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants.pdf (2.26 MB)
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Data_Sheet_1_Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants.pdf

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posted on 02.06.2022, 05:00 authored by Tingting Li, Bingjie Zhou, Zhipu Luo, Yanling Lai, Suqiong Huang, Yuanze Zhou, Yaning Li, Anupriya Gautam, Salome Bourgeau, Shurui Wang, Juan Bao, Jingquan Tan, Dimitri Lavillette, Dianfan Li

SARS-CoV-2 and its variants, such as the Omicron continue to threaten public health. The virus recognizes the host cell by attaching its Spike (S) receptor-binding domain (RBD) to the host receptor, ACE2. Therefore, RBD is a primary target for neutralizing antibodies and vaccines. Here, we report the isolation and biological and structural characterization of a single-chain antibody (nanobody) from RBD-immunized alpaca. The nanobody, named DL28, binds to RBD tightly with a KD of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 μg mL−1. Neutralization assays with a panel of variants of concern (VOCs) reveal its wide-spectrum activity with IC50 values ranging from 0.35 to 1.66 μg mL−1 for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 μg mL−1 for the currently prevalent Omicron. Competition binding assays show that DL28 blocks ACE2-binding. However, structural characterizations and mutagenesis suggest that unlike most antibodies, the blockage by DL28 does not involve direct competition or steric hindrance. Rather, DL28 may use a “conformation competition” mechanism where it excludes ACE2 by keeping an RBD loop in a conformation incompatible with ACE2-binding.

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