Neutralization mechanism of a highly potent antibody against Zika virus

Nat Commun. 2016 Nov 24;7:13679. doi: 10.1038/ncomms13679.


The rapid spread of Zika virus (ZIKV), which causes microcephaly and Guillain-Barré syndrome, signals an urgency to identify therapeutics. Recent efforts to rescreen dengue virus human antibodies for ZIKV cross-neutralization activity showed antibody C10 as one of the most potent. To investigate the ability of the antibody to block fusion, we determined the cryoEM structures of the C10-ZIKV complex at pH levels mimicking the extracellular (pH8.0), early (pH6.5) and late endosomal (pH5.0) environments. The 4.0 Å resolution pH8.0 complex structure shows that the antibody binds to E proteins residues at the intra-dimer interface, and the virus quaternary structure-dependent inter-dimer and inter-raft interfaces. At pH6.5, antibody C10 locks all virus surface E proteins, and at pH5.0, it locks the E protein raft structure, suggesting that it prevents the structural rearrangement of the E proteins during the fusion event-a vital step for infection. This suggests antibody C10 could be a good therapeutic candidate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / ultrastructure
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / ultrastructure
  • Cross Reactions / immunology
  • Cryoelectron Microscopy
  • Dengue Virus / immunology
  • Hydrogen-Ion Concentration
  • Viral Envelope Proteins / immunology*
  • Zika Virus / immunology*
  • Zika Virus / ultrastructure


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Envelope Proteins