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TitleUltrapotent human antibodies lock E protein dimers central region of diverse DENV3 morphological variants.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 9182, Year 2025
Publish dateOct 16, 2025
AuthorsGuntur Fibriansah / Thiam-Seng Ng / Xin-Ni Lim / Anastasia Shebanova / Lee Ching Ng / Song Ling Tan / Aaron W K Tan / Jian Shi / James E Crowe / Shee-Mei Lok /
PubMed AbstractDengue virus (DENV) consists of four serotypes (DENV1-4). Current vaccines induce differing levels of immune response against the four serotypes, that might prime recipients to develop severe disease ...Dengue virus (DENV) consists of four serotypes (DENV1-4). Current vaccines induce differing levels of immune response against the four serotypes, that might prime recipients to develop severe disease in subsequent infections. Several DENV tetravalent vaccine clinical trials suggested an increased incidence in severe DENV3 cases, suggesting a need to develop DENV3 therapeutics. Human monoclonal antibodies (HMAbs) DENV-290 and DENV-115 are ultrapotent against diverse DENV3 strains with differing particle morphologies. They mainly neutralize by inhibition of virus attachment to cells. CryoEM structures of Fabs complexed with differing DENV3 morphological variants show their Fabs binding across two E protein protomers at the center of the E dimer. This new class of E protein dimer binding antibodies is named EDE-C. The cryoEM structures also show how IgGs engage the DENV particles. Results define the structural and molecular basis for the ultrapotent activity of EDE-C antibodies.
External linksNat Commun / PubMed:41102151 / PubMed Central
MethodsEM (single particle) / EM (helical sym.)
Resolution3.3 - 11.0 Å
Structure data

EMDB-36429, PDB-8jn1:
Cryo-EM structure of dengue virus serotype 3 strain EHIE46200Y19 in complex with human antibody DENV-115 IgG at 4 deg C (subparticle LLR-LRR)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-36430, PDB-8jn2:
Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-115 Fab at 4 deg C (subparticle LLR-LRR)
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-36431, PDB-8jn3:
Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-115 Fab at 37 deg C (subparticle LLR-LRR)
Method: EM (single particle) / Resolution: 5.4 Å

EMDB-36432, PDB-8jn4:
Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-290 Fab at 4 deg C (subparticle LLR-LRR)
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-36433, PDB-8jn5:
Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-290 Fab at 37 deg C (subparticle LLR-LRR)
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-36434, PDB-8jn6:
Cryo-EM structure of the small tail club shape particle of dengue virus serotype 3 strain CH53489 in complex with human antibody DENV-290 Fab at 37 deg C
Method: EM (helical sym.) / Resolution: 9.8 Å

EMDB-36435, PDB-8jn7:
Cryo-EM structure of the big tail club shape particle of dengue virus serotype 3 strain CH53489 in complex with human antibody DENV-290 Fab at 37 deg C
Method: EM (helical sym.) / Resolution: 11.0 Å

EMDB-36436: Cryo-EM structure of dengue virus serotype 3 strain EHIE46200Y19 in complex with human antibody DENV-115 IgG at 4 deg C
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-36437: Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-115 Fab at 4 deg C
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-36438: Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-115 Fab at 37 deg C
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-36439: Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-290 Fab at 4 deg C
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-36440: Cryo-EM structure of dengue virus serotype 3 strain 863DK in complex with human antibody DENV-290 Fab at 37 deg C
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-36441: Cryo-EM structure of dengue virus serotype 3 strain CH53489 spherical particle in complex with human antibody DENV-290 Fab at 37 deg C
Method: EM (single particle) / Resolution: 5.6 Å

Source
  • Aedes albopictus (Asian tiger mosquito)
  • homo sapiens (human)
  • dengue virus type 3
KeywordsVIRUS / dengue virus / human antibody / dengue-antibody structure / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex

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