Neutralization Mechanism of a Highly Potent Antibody Against Zika Virus

Overview

Journal Nat Commun

Specialty Biology

Date 2016 Nov 25

PMID 27882950

Citations 66

Authors

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

Affiliations

Soon will be listed here.

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.

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