8ZRD

The complex structure of SARS-CoV-2 RBD and llama single-domain antibody S4

Summary for 8ZRD

• Entry DOI: 10.2210/pdb8zrd/pdb
• Descriptor: Spike protein S1, llama single-domain antibody S4, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: sars-cov-2, llama single-domain antibody, viral protein/immune system, viral protein-immune system complex
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 4
• Total formula weight: 82221.54

Authors

Chen, L. (deposition date: 2024-06-04, release date: 2025-09-10, Last modification date: 2026-02-11)

Primary citation

Liu, C.,Hadiatullah, H.,Yuchi, Z.
Identification of a potent SARS-CoV-2 neutralizing nanobody targeting the receptor-binding domain of the spike protein.
Int.J.Biol.Macromol., 281:136403-136403, 2024

PubMed Abstract: SARS-CoV-2 and its variants continue to pose a significant threat to public health. Nanobodies (Nbs) that inhibit the interaction between the receptor-binding domain (RBD) of the spike protein and the host cell receptor angiotensin-converting enzyme 2 (ACE2) are promising drug candidates. In this study, we report the discovery and structural characterization of a potent Nb that targets the RBD. By screening a phage display alpaca naive Nbs library using the RBD as bait, we identified sixteen candidate Nbs. Of these, nine exhibited nanomolar to micromolar binding affinity and strong neutralizing activity against pseudotyped SARS-CoV-2 viruses, with NbS4 showing the highest neutralization potency. The crystal structure of the SARS-CoV-2 RBD in complex with NbS4 revealed that this Nb binds to a site partially overlapping the ACE2 binding region. Importantly, the key binding residues of NbS4 in the RBD are conserved across most known variants, making it a promising candidate for COVID-19 treatment.

PubMed: 39383917
DOI: 10.1016/j.ijbiomac.2024.136403

Experimental method

X-RAY DIFFRACTION (2.715 Å)