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Zika virus (ZIKV), a mosquito-borne flavivirus, is a current global public health concern. The flavivirus envelope (E) glycoprotein is responsible for virus entry and represents a major target of neutralizing antibodies for other flaviviruses. Here, we report the structures of ZIKV E protein at 2.0 Å and in complex with a flavivirus broadly neutralizing murine antibody 2A10G6 at 3.0 Å. ZIKV-E resembles all the known flavivirus E structures but contains a unique, positively charged patch adjacent to the fusion loop region of the juxtaposed monomer, which may influence host attachment. The ZIKV-E-2A10G6 complex structure reveals antibody recognition of a highly conserved fusion loop. 2A10G6 binds to ZIKV-E with high affinity in vitro and neutralizes currently circulating ZIKV strains in vitro and in mice. The E protein fusion loop epitope represents a potential candidate for therapeutic antibodies against ZIKV.
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•Report structures of ZIKV E protein and its complex with a broadly neutralizing antibody•ZIKV-E contains a unique, positively charged patch, which may influence host attachment•The ZIKV-E-antibody structure reveals antibody recognition of a conserved fusion loop•Antibody binds ZIKV-E and neutralizes circulating ZIKV strains in vitro and in mice
Zika virus (ZIKV) is a mosquito-borne flavivirus. Dai et al. report the structures of ZIKV envelope (E) protein and its complex with a flavivirus broadly protective antibody, which reveals antibody recognition of a conserved fusion loop. Antibody binds to ZIKV-E with high affinity and neutralizes currently circulating ZIKV strains in mice.