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PDBsum entry 4c1w
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Sugar binding protein
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PDB id
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4c1w
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References listed in PDB file
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Key reference
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Title
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Prevention of influenza by targeting host receptors using engineered proteins.
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Authors
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H.Connaris,
E.A.Govorkova,
Y.Ligertwood,
B.M.Dutia,
L.Yang,
S.Tauber,
M.A.Taylor,
N.Alias,
R.Hagan,
A.A.Nash,
R.G.Webster,
G.L.Taylor.
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Ref.
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Proc Natl Acad Sci U S A, 2014,
111,
6401-6406.
[DOI no: ]
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PubMed id
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Abstract
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There is a need for new approaches for the control of influenza given the burden
caused by annual seasonal outbreaks, the emergence of viruses with pandemic
potential, and the development of resistance to current antiviral drugs. We show
that multivalent biologics, engineered using carbohydrate-binding modules
specific for sialic acid, mask the cell-surface receptor recognized by the
influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1
influenza virus. The most promising biologic protects mice when given as a
single 1-μg intranasal dose 7 d in advance of viral challenge. There also is
sufficient virus replication to establish an immune response, potentially
protecting the animal from future exposure to the virus. Furthermore, the
biologics appear to stimulate inflammatory mediators, and this stimulation may
contribute to their protective ability. Our results suggest that this
host-targeted approach could provide a front-line prophylactic that has the
potential to protect against any current and future influenza virus and possibly
against other respiratory pathogens that use sialic acid as a receptor.
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