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TitleStructural basis for antibody cross-neutralization of Dengue and Zika viruses.
Journal, issue, pagesCommun Biol, Vol. 9, Issue 1, Year 2026
Publish dateMar 10, 2026
AuthorsNicholas K Hurlburt / Jay Lubow / Leslie Goo / Marie Pancera /
PubMed AbstractSafe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of Dengue virus (DenV1-4) must elicit broadly neutralizing ...Safe and effective vaccines against co-circulating mosquito-borne orthoflaviviruses such as Zika virus (ZikV) and the four serotypes of Dengue virus (DenV1-4) must elicit broadly neutralizing antibodies (bnAbs) to prevent the risk of enhancement of infection by non-neutralizing antibodies. We recently discovered new orthoflavivirus-directed bnAbs, including F25.S02, which neutralizes DenV1-4 and ZikV with comparable or superior potency to the previously characterized E dimer epitope (EDE) bnAbs. Here, we used cryoEM and X-ray crystallography to understand the basis of cross-neutralization of F25.S02 at the molecular level. We obtained a ~ 4.2 Å cryoEM structure of F25.S02 Fab bound to a stabilized DenV3 soluble E protein dimer and a 2.3 Å crystal structure of F25.S02 Fab bound to ZikV soluble E protein dimer. Like previously described EDE1 bnAbs, the structural epitope of F25.S02 is at the E dimer interface, encompassing predominantly conserved regions in domain II, including the fusion loop. However, unlike EDE1 bnAbs, F25.S02 binding is almost entirely dependent on the heavy chain and is shifted slightly away from the dimer symmetry axis. Our findings emphasize the importance of this cross-neutralizing site of vulnerability for DenV and ZikV that can facilitate rational design of vaccines and therapeutics.
External linksCommun Biol / PubMed:41807764 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.3 - 4.16 Å
Structure data

EMDB-70931: CryoEM structure of stabilized dengue 3 virus envelope glycoprotein in complex with Fab of F25.S01
PDB-9owe: CryoEM structure of stabilized dengue 3 virus envelope glycoprotein in complex with Fab of F25.S02
Method: EM (single particle) / Resolution: 4.16 Å

PDB-9owf:
X-ray crystal structure of Zika virus envelope glycoprotein in complex with Fab of F25.S02
Method: X-RAY DIFFRACTION / Resolution: 2.3 Å

Chemicals

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

ChemComp-HOH:
WATER

Source
  • homo sapiens (human)
  • dengue virus type 3
  • zika virus
KeywordsIMMUNE SYSTEM / Orthoflavivirus / Dengue / Zika

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