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TitleMechanism of an RBM-targeted rabbit monoclonal antibody 9H1 neutralizing SARS-CoV-2.
Journal, issue, pagesBiochem Biophys Res Commun, Vol. 660, Page 43-49, Year 2023
Publish dateApr 5, 2023
AuthorsXiaoyu Chu / Xinyu Ding / Yixuan Yang / Yuchi Lu / Tinghan Li / Yan Gao / Le Zheng / Hang Xiao / Tingting Yang / Hao Cheng / Haibin Huang / Yang Liu / Yang Lou / Chao Wu / Yuxin Chen / Haitao Yang / Xiaoyun Ji / Hangtian Guo /
PubMed AbstractThe COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant ...The COVID-19 pandemic, caused by SARS-CoV-2, has led to over 750 million infections and 6.8 million deaths worldwide since late 2019. Due to the continuous evolution of SARS-CoV-2, many significant variants have emerged, creating ongoing challenges to the prevention and treatment of the pandemic. Therefore, the study of antibody responses against SARS-CoV-2 is essential for the development of vaccines and therapeutics. Here we perform single particle cryo-electron microscopy (cryo-EM) structure determination of a rabbit monoclonal antibody (RmAb) 9H1 in complex with the SARS-CoV-2 wild-type (WT) spike trimer. Our structural analysis shows that 9H1 interacts with the receptor-binding motif (RBM) region of the receptor-binding domain (RBD) on the spike protein and by directly competing with angiotensin-converting enzyme 2 (ACE2), it blocks the binding of the virus to the receptor and achieves neutralization. Our findings suggest that utilizing rabbit-derived mAbs provides valuable insights into the molecular interactions between neutralizing antibodies and spike proteins and may also facilitate the development of therapeutic antibodies and expand the antibody library.
External linksBiochem Biophys Res Commun / PubMed:37062240 / PubMed Central
MethodsEM (single particle)
Resolution3.5 - 3.59 Å
Structure data

34686

8heb

EMDB-34686, PDB-8heb:
SARS-CoV-2 Spike trimer in complex with RmAb 9H1 Fab in the class 1 conformation
Method: EM (single particle) / Resolution: 3.53 Å

34687

8hec

EMDB-34687, PDB-8hec:
SARS-CoV-2 Spike trimer in complex with RmAb 9H1 Fab in the class 2 conformation
Method: EM (single particle) / Resolution: 3.5 Å

34688

8hed

EMDB-34688, PDB-8hed:
Local refinement of the SARS-CoV-2 Spike trimer in complex with RmAb 9H1 Fab
Method: EM (single particle) / Resolution: 3.59 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

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

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