Neutralization mechanism of a highly potent antibody against Zika virus

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 () and Shee-Mei Lok ()
Additional contact information
Shuijun Zhang: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Victor A. Kostyuchenko: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Thiam-Seng Ng: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Xin-Ni Lim: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Justin S. G. Ooi: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Sebastian Lambert: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Ter Yong Tan: Program in Emerging Infectious Diseases, Duke–National University of Singapore Medical School
Douglas G. Widman: University of North Carolina at Chapel Hill
Jian Shi: Centre for BioImaging Sciences, 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

Nature Communications, 2016, vol. 7, issue 1, 1-7

Abstract: 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.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms13679 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13679

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms13679

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().