Reference
Reference TypeLiterature
IEDB_Reference:1046220
TitleStructure and function of an unusual R452-dependent monoclonal antibody against SARS-CoV-2.
AuthorsBing Zhou; Qi Gui; Congcong Liu; Huimin Guo; Haiyan Wang; Lin Cheng; Qing Fan; Xiangyang Ge; Zheng Zhang; Bin Ju
AffiliationsInstitute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China; Department of Infectious Diseases, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China; Guangdong Key Laboratory for Anti-infection Drug Quality Evaluation, Shenzhen, Guangdong, China; Shenzhen Research Center for Communicable Disease Diagnosis and Treatment, Chinese Academy of Medical Sciences, Shenzhen, Guangdong, China.
JournalJ Virol
PMID:40197058
Year2025
AbstractThe coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is still a major public health concern worldwide. Currently, SARS-CoV-2 variants have been widely used to develop the updated vaccine. However, whether these mutated residues still have good immunogenicity remains elusive. In particular, we know little about what kind of antibodies can be induced by the infection or vaccination of SARS-CoV-2 variants and their biological characteristics. Here, we identified an R452-dependent monoclonal neutralizing antibody, ConD-852, from a primarily Delta variant-infected individual, indicating that the mutated R452 residue has good immunogenicity. We determined the high-resolution cryo-electron microscopy (cryo-EM) structure of ConD-852 complexed with the Delta receptor-binding domain (RBD), revealing how it binds to the R452-related epitopes and their detailed interactions. Interestingly, ConD-852 could only bind to the amino acid residue "R" at the 452 position on RBD, displaying a strict restriction to recognize SARS-CoV-2. Overall, our findings regarding ConD-852 confirmed the good immunogenicity of SARS-CoV-2 variants carrying the L452R mutation and enriched our knowledge of the binding model involving the neutralizing antibody and the mutated virus.IMPORTANCEAlthough SARS-CoV-2 variants have been widely used to update the COVID-19 vaccine candidate, whether these mutations still have good immunogenicity is unknown. This study demonstrates that the mutated R452 residue can induce potent neutralizing antibodies and reports a high-resolution cryo-EM structure of an R452-dependent monoclonal antibody binding to the epitopes around the R452 residue on SARS-CoV-2 RBD.
Curation Last Updated2025-04-17 20:01:02
Epitope
Epitope ID2275973
IEDB_epitope:2275973
Chemical TypeDiscontinuous peptide
Source Namesurface glycoprotein [Severe acute respiratory syndrome coronavirus 2]
GenPept:UEO57867.1
Source OrganismSARS-CoV2 Delta
Discontinuous ResiduesT413, G414, K415, D418, Y419, Y451, L453, R455, K456, N458, Y471, A473, G474, S475, F484, N485, Y487, Q491, Y503
Epitope Reference Details
Epitope Structure DefinesPartial Epitope
Epitope NameEpitope of Fab P2C-1F11 on Delta RBD
Reference RegionT415, G416, K417, D420, Y421, Y453, L455, R457, K458, N460, Y473, A475, G476, S477, F486, N487, Y489, Q493, Y505
CommentsThe epitope residues were calculated from [PDB: 9L6C] as the antigen residues at 4Å atomic distance from the antibody.
Location of Data in ReferencePDB 9L6C
Immunization
Host OrganismHomo sapiens (human)
NCBITaxon:9606
Host Details
Host GeolocationChina [ID: GAZ_00002845]
GAZ:00002845
1st In Vivo Process
In Vivo Process TypeOccurrence of infectious disease
ONTIE:0003317
Disease StateCOVID-19
DOID:0080600
Disease StagePost;
ONTIE:0003544
1st Immunogen
Epitope RelationTaxonomic Parent
Object TypeOrganism
OrganismSARS-CoV2
NCBITaxon:2697049
Immunization Comments
Immunization CommentsGeneration of the mAb was described in the cited reference [PMID: 32454513]. Blood samples were collected from eight patients infected with SARS-CoV-2 in January 2020 during the early outbreak in Shenzhen. Flow cytometry was used to isolate RBD-binding B cells. The IgG heavy and light chain variable genes were cloned into expression vectors to produce full IgG1 antibodies.
B Cell Assay
Qualitative MeasurementPositive
Method/TechniqueELISA
OBI:0001657
Measurement ofqualitative binding
Assayed Antibody
Assayed Antibody Source MaterialPurified Immunoglobulin
Assayed Antibody Immunoglobulin DomainEntire Antibody
Assayed Antibody Purification StatusMonoclonal
Assayed Antibody NameP2C-1F11
Assayed Antibody Heavy Chain TypeIgG1
Assayed Antibody Light Chain TypeKappa
Assayed Antibody Object
Chemical TypeMulti-Chain protein
Chain 1 Accession NameChain D, Heavy chain of Fab P2C-1F11
GenPept:9L6C_D
Source OrganismHomo sapiens (human)
NCBITaxon:9606
Molecule NameP2C-1F11
Chain 2 NameChain F, Light chain of Fac P2C-1F11
GenPept:9L6C_F
Source OrganismHomo sapiens (human)
NCBITaxon:9606
Antigen
Epitope RelationFragment of Source Antigen
Chemical TypeLinear peptide
Linear SequenceRVQPTESIVRFPNITNLCPFGEVFNATRFASVYAWNRKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRGDEVRQIAPGQTGKIADYNYKLPDDFTGCVIAWNSNNLDSKVGGNYNYRYRLFRKSNLKPFERDISTEIYQAGSKPCNGVEGFNCYFPLQSYGFQPTNGVGYQPYRVVVLSFELLHAPATVCGPKKSTNLVKNKCVNF
Source Molecule Namesurface glycoprotein [Severe acute respiratory syndrome coronavirus 2]
GenPept:UEO57867.1
Source OrganismSARS-CoV2 Delta
Starting Position317
Ending Position539
Antigen Details
Antigen Reference NameDelta RBD
Assay Reference Details
Assay Comments by IEDB CuratorThe epitope specific mAb bound the SARS-CoV2 Delta RBD as demonstrated by ELISA.
Location of Assay Data in ReferenceFigure 2