Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Frontiers in Microbiology Année : 2022

Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants

Zhipu Luo
  • Fonction : Auteur
Yuanze Zhou
  • Fonction : Auteur
Shurui Wang
  • Fonction : Auteur
Jingquan Tan
  • Fonction : Auteur

Résumé

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 K-D of 1.56 nM and neutralizes the original SARS-CoV-2 strain with an IC50 of 0.41 mu g 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 mu g mL(-1) for the Alpha/Beta/Gamma/Delta and an IC50 of 0.66 mu g 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.
Fichier principal
Vignette du fichier
pdf (2.87 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03763326 , version 1 (20-01-2023)

Licence

Paternité

Identifiants

Citer

Tingting Li, Bingjie Zhou, Zhipu Luo, Yanling Lai, S Huang, et al.. Structural Characterization of a Neutralizing Nanobody With Broad Activity Against SARS-CoV-2 Variants. Frontiers in Microbiology, 2022, 13, ⟨10.3389/fmicb.2022.875840⟩. ⟨hal-03763326⟩
33 Consultations
13 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More