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Neutralization mechanism of a highly potent antibody against Zika virus

Author

Listed:
  • Shuijun Zhang

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Victor A. Kostyuchenko

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Thiam-Seng Ng

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Xin-Ni Lim

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Justin S. G. Ooi

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Sebastian Lambert

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Ter Yong Tan

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

  • Douglas G. Widman

    (University of North Carolina at Chapel Hill)

  • Jian Shi

    (Centre for BioImaging Sciences, National University of Singapore
    CryoEM unit, National University of Singapore)

  • Ralph S. Baric

    (University of North Carolina at Chapel Hill)

  • Shee-Mei Lok

    (Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
    Centre for BioImaging Sciences, National University of Singapore)

Abstract

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.

Suggested Citation

  • Shuijun Zhang & Victor A. Kostyuchenko & Thiam-Seng Ng & Xin-Ni Lim & Justin S. G. Ooi & Sebastian Lambert & Ter Yong Tan & Douglas G. Widman & Jian Shi & Ralph S. Baric & Shee-Mei Lok, 2016. "Neutralization mechanism of a highly potent antibody against Zika virus," Nature Communications, Nature, vol. 7(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13679
    DOI: 10.1038/ncomms13679
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