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TitleMechanism of a rabbit monoclonal antibody broadly neutralizing SARS-CoV-2 variants.
Journal, issue, pagesCommun Biol, Vol. 6, Issue 1, Page 364, Year 2023
Publish dateApr 3, 2023
AuthorsHangtian Guo / Yixuan Yang / Tiantian Zhao / Yuchi Lu / Yan Gao / Tinghan Li / Hang Xiao / Xiaoyu Chu / Le Zheng / Wanting Li / Hao Cheng / Haibin Huang / Yang Liu / Yang Lou / Henry C Nguyen / Chao Wu / Yuxin Chen / Haitao Yang / Xiaoyun Ji /
PubMed AbstractDue to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a ...Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.
External linksCommun Biol / PubMed:37012333 / PubMed Central
MethodsEM (single particle)
Resolution3.41 - 3.7 Å
Structure data

34406

8gzz

EMDB-34406, PDB-8gzz:
Local refinement of SARS-CoV-2 Omicron BA.1 Spike glycoprotein in complex with rabbit monoclonal antibody 1H1 Fab
Method: EM (single particle) / Resolution: 3.52 Å

34407

8h00

EMDB-34407, PDB-8h00:
SARS-CoV-2 Omicron BA.1 Spike glycoprotein in complex with rabbit monoclonal antibody 1H1 Fab in the class 1 conformation
Method: EM (single particle) / Resolution: 3.41 Å

34408

8h01

EMDB-34408, PDB-8h01:
SARS-CoV-2 Omicron BA.1 Spike glycoprotein in complex with rabbit monoclonal antibody 1H1 Fab in class 2 conformation
Method: EM (single particle) / Resolution: 3.7 Å

35328

8itu

EMDB-35328: cryo-EM density map of SARS-CoV-2 Omicron BA.1 spike in complex with RmAb 1H1 IgG
PDB-8itu: SARS-CoV-2 Omicron BA.1 Spike glycoprotein in complex with rabbit monoclonal antibody 1H1 IgG.
Method: EM (single particle) / Resolution: 3.68 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • severe acute respiratory syndrome coronavirus 2
  • oryctolagus cuniculus (rabbit)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM COMPLEX

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