title: Neutralization mechanism of a highly potent antibody against Zika virus.
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.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Kostyuchenko
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Thiam-Seng
authors.initials: TS
authors.lastname: Ng
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Xin-Ni
authors.initials: XN
authors.lastname: Lim
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Justin S G
authors.initials: JSG
authors.lastname: Ooi
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Lambert
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Ter Yong
authors.initials: TY
authors.lastname: Tan
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7435, USA.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Widman
authors.affiliation: Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.|CryoEM unit, Department of Biological Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7435, USA.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.|Centre for BioImaging Sciences, National University of Singapore, Singapore 117557, Singapore.
authors.forename: Shee-Mei
authors.initials: SM
authors.lastname: Lok
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology* / Q000648:ultrastructure; D000914:Antibodies, Viral / Q000276:immunology* / Q000648:ultrastructure; D003429:Cross Reactions / Q000276:immunology; D020285:Cryoelectron Microscopy; D003716:Dengue Virus / Q000276:immunology; D006863:Hydrogen-Ion Concentration; D014759:Viral Envelope Proteins / Q000276:immunology*; D000071244:Zika Virus / Q000276:immunology* / Q000648:ultrastructure
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins