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Structural insights into the design of novel anti-influenza therapies

Nature Structural & Molecular Biology volume 25, pages 115–121 (2018)Cite this article

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Abstract

A limited arsenal of therapies is currently available to tackle the emergence of a future influenza pandemic or even to deal effectively with the continual outbreaks of seasonal influenza. However, recent findings hold great promise for the design of novel vaccines and therapeutics, including the possibility of more universal treatments. Structural biology has been a major contributor to those advances, in particular through the many studies on influenza hemagglutinin (HA), the major surface antigen. HA’s primary function is to enable the virus to enter host cells, and structural work has revealed the various HA conformational forms generated during the entry process. Other studies have explored how human broadly neutralizing antibodies (bnAbs), designed proteins, peptides and small molecules, can inhibit and neutralize the virus. Here we review milestones in HA structural biology and how the recent insights from bnAbs are paving the way to design novel vaccines and therapeutics.

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Fig. 1: Milestones of influenza HA structural biology.
Fig. 2: Anti-HA broadly neutralizing antibodies (bnAbs).
Fig. 3: HA stem immunogen design.
Fig. 4: Protein and peptide design that target the HA stem region.
Fig. 5: Protein and peptide design that targets the HA receptor-binding site (RBS).
Fig. 6: Inhibition of HA-mediated membrane fusion by small molecules.

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Acknowledgements

We appreciate support from NIH R56 AI127371 (I.A.W.) and a Croucher Foundation Fellowship (N.C.W.).

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  1. Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA, USA

    Nicholas C. Wu & Ian A. Wilson

  2. The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, USA

    Ian A. Wilson

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Wu, N.C., Wilson, I.A. Structural insights into the design of novel anti-influenza therapies. Nat Struct Mol Biol 25, 115–121 (2018). https://doi.org/10.1038/s41594-018-0025-9

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