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Structure paper

TitleDiscovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 3537, Year 2023
Publish dateJun 15, 2023
AuthorsYu Guo / Guangshun Zhang / Qi Yang / Xiaowei Xie / Yang Lu / Xuelian Cheng / Hui Wang / Jingxi Liang / Jielin Tang / Yuxin Gao / Hang Shang / Jun Dai / Yongxia Shi / Jiaxi Zhou / Jun Zhou / Hangtian Guo / Haitao Yang / Jianwei Qi / Lijun Liu / Shihui Ma / Biao Zhang / Qianyu Huo / Yi Xie / Junping Wu / Fang Dong / Song Zhang / Zhiyong Lou / Yan Gao / Zidan Song / Wenming Wang / Zixian Sun / Xiaoming Yang / Dongsheng Xiong / Fengjiang Liu / Xinwen Chen / Ping Zhu / Ximo Wang / Tao Cheng / Zihe Rao /
PubMed AbstractThe SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, ...The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2-5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.
External linksNat Commun / PubMed:37322000 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.51 - 3.8 Å
Structure data

34124

7yve

EMDB-34124, PDB-7yve:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH027 Fab
Method: EM (single particle) / Resolution: 3.4 Å

34125

7yvf

EMDB-34125, PDB-7yvf:
Omicron BA.4/5 SARS-CoV-2 S RBD in complex with TH027 Fab
Method: EM (single particle) / Resolution: 3.4 Å

34126

7yvg

EMDB-34126, PDB-7yvg:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH132 Fab
Method: EM (single particle) / Resolution: 3.4 Å

34127

7yvh

EMDB-34127, PDB-7yvh:
Omicron BA.4/5 SARS-CoV-2 S RBD in complex with TH132 Fab
Method: EM (single particle) / Resolution: 3.6 Å

34128

7yvi

EMDB-34128, PDB-7yvi:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH236 Fab
Method: EM (single particle) / Resolution: 3.7 Å

34129

7yvj

EMDB-34129, PDB-7yvj:
Omicron BA.4/5 SARS-CoV-2 S RBD in complex with TH236 Fab
Method: EM (single particle) / Resolution: 3.6 Å

34130

7yvk

EMDB-34130, PDB-7yvk:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH272 Fab
Method: EM (single particle) / Resolution: 3.2 Å

34131

7yvl

EMDB-34131, PDB-7yvl:
Omicron BA.4/5 SARS-CoV-2 S RBD in complex with TH272 Fab
Method: EM (single particle) / Resolution: 3.3 Å

34132

7yvm

EMDB-34132, PDB-7yvm:
Omicron BA.4/5 SARS-CoV-2 S RBD in complex with TH272 Fab
Method: EM (single particle) / Resolution: 3.5 Å

34133

7yvn

EMDB-34133, PDB-7yvn:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH281 Fab
Method: EM (single particle) / Resolution: 3.4 Å

34134

7yvo

EMDB-34134, PDB-7yvo:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH027/132 Fab
Method: EM (single particle) / Resolution: 3.3 Å

34135

7yvp

EMDB-34135, PDB-7yvp:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH272/281 Fab
Method: EM (single particle) / Resolution: 3.8 Å

34181

8gou

EMDB-34181, PDB-8gou:
Omicron BA.4/5 SARS-CoV-2 S in complex with TH003 Fab
Method: EM (single particle) / Resolution: 3.7 Å

PDB-8gpy:
Crystal structure of Omicron BA.4/5 RBD in complex with a neutralizing antibody scFv
Method: X-RAY DIFFRACTION / Resolution: 2.51 Å

Chemicals

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

ChemComp-HOH:
WATER / Water

Source
  • severe acute respiratory syndrome coronavirus 2
  • homo sapiens (human)
KeywordsVIRAL PROTEIN/ANTIVIRAL PROTEIN / COVID-19 / spike glycoprotein / virus / VIRAL PROTEIN / VIRAL PROTEIN-ANTIVIRAL PROTEIN complex / ANTIVIRAL PROTEIN/VIRAL PROTEIN / ANTIVIRAL PROTEIN-VIRAL PROTEIN complex / Omicron / crystal strcture / neutralizing antibody / scFV

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