ISDA: 8H5T

Deposition Date 2022-10-13

Release Date 2023-10-18

Last Version Date 2026-03-11

Entry Detail

PDB ID:

8H5T

Keywords:

VIRAL PROTEIN

Title:

Crystal structure of SARS-CoV-2 spike receptor-binding domain in complex with neutralizing nanobody Nb-015

Biological Source:

Source Organism(s):

Severe acute respiratory syndrome coronavirus 2 (Taxon ID: 2697049)
Vicugna pacos (Taxon ID: 30538)

Expression System(s):

Spodoptera frugiperda, Brevibacillus choshinensis

Method Details:

Experimental Method:

X-RAY DIFFRACTION

Resolution:

2.00 Å

R-Value Free:

0.20

R-Value Work:

0.17

R-Value Observed:

0.17

Space Group:

I 41

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Macromolecular Entities

Structures with similar UniProt ID

Protein Blast

Polymer Type:polypeptide(L)
Molecule:Spike protein S1
Gene (Uniprot):S
Chain IDs:A
Chain Length:218
Number of Molecules:1
Biological Source:Severe acute respiratory syndrome coronavirus 2

UniProt ID:P0DTC2 Pfam ID:PF09408

Polymer Type:polypeptide(L)
Molecule:Nanobody Nb-015
Chain IDs:B
Chain Length:127
Number of Molecules:1
Biological Source:Vicugna pacos

Ligand Molecules

NAG

Primary Citation

Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization.

Yang, J, Lin, S, Chen, Z, Yang, F, Guo, L, Wang, L, Duan, Y, Zhang, X, Dai, Y, Yin, K, Yu, C, Yuan, X, Sun, H, He, B, Cao, Y, Ye, H, Dong, H, Liu, X, Chen, B, Li, J, Zhao, Q, Lu, G.Show

Plos Pathog. 19 e1011804 e1011804 (2023)

PMID: 38033141 DOI: 10.1371/journal.ppat.1011804

Abstact

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and profound immune-escape capacity makes it an urgent need to develop broad-spectrum therapeutics. Nanobodies have recently attracted extensive attentions due to their excellent biochemical and binding properties. Here, we report two high-affinity nanobodies (Nb-015 and Nb-021) that target non-overlapping epitopes in SARS-CoV-2 S-RBD. Both nanobodies could efficiently neutralize diverse viruses of SARS-CoV-2. The neutralizing mechanisms for the two nanobodies are further delineated by high-resolution nanobody/S-RBD complex structures. In addition, an Fc-based tetravalent nanobody format is constructed by combining Nb-015 and Nb-021. The resultant nanobody conjugate, designated as Nb-X2-Fc, exhibits significantly enhanced breadth and potency against all-tested SARS-CoV-2 variants, including Omicron sub-lineages. These data demonstrate that Nb-X2-Fc could serve as an effective drug candidate for the treatment of SARS-CoV-2 infection, deserving further in-vivo evaluations in the future.

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Primary Citation of related structures

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