8H5U

Crystal structure of SARS-CoV-2 spike receptor-binding domain in complex with neutralizing nanobody Nb-021

Summary for 8H5U

• Entry DOI: 10.2210/pdb8h5u/pdb
• Descriptor: Spike protein S1, Nanobody Nb-021, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: viral protein, immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 4
• Total formula weight: 75360.93

Authors

Yang, J.,Lin, S.,Lu, G.W. (deposition date: 2022-10-13, release date: 2023-10-18, Last modification date: 2024-11-20)

Primary citation

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.
Development of a bispecific nanobody conjugate broadly neutralizes diverse SARS-CoV-2 variants and structural basis for its broad neutralization.
Plos Pathog., 19:e1011804-e1011804, 2023

PubMed Abstract: 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.

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

Experimental method

X-RAY DIFFRACTION (2.401 Å)