National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI076331
United States
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI073755
United States
Citation
Journal: Viruses / Year: 2020 Title: Structural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections. Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G ...Authors: Madhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G Rossmann / Richard J Kuhn / Abstract: Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We ...Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.
History
Deposition
Oct 7, 2020
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Header (metadata) release
Dec 16, 2020
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Map release
Dec 16, 2020
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Update
Dec 16, 2020
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Current status
Dec 16, 2020
Processing site: RCSB / Status: Released
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Structure visualization
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Surface view with section colored by density value
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