Volume 95 Issue 26 | p. 8 | Concentrates
Issue Date: June 26, 2017

Three-pronged designed peptide neutralizes influenza

Researchers improve on nature by finding a way to block viral binding to hosts at three spots on the pathogen simultaneously
Department: Science & Technology
Keywords: infectious disease, synthetic biology, influenza
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A designed protein (brown and orange) binds the influenza hemagglutinin protein (green) at three locations simultaneously to block infection.
Credit: David Baker/U Washington
This schematic shows how a customized peptide binds to the influenza hemagglutinin protein.
 
A designed protein (brown and orange) binds the influenza hemagglutinin protein (green) at three locations simultaneously to block infection.
Credit: David Baker/U Washington

If you want to thwart infection by influenza viruses, a good bet is to block the pathogen’s exterior hemagglutinin proteins from binding with a host cell’s sialic acid-containing sugars. Nature already uses this interference strategy: Antibodies bind influenza hemagglutinin, preventing infection by obstructing the host-pathogen interaction in a variety of ways, sometimes at the sialic acid binding site and other times with just the antibody’s sheer physical bulk. This bulk has its downside, though: Only one antibody can bind a hemagglutinin site at a time. David Baker and Eva-Maria Strauch of the University of Washington and colleagues wondered if they could design a protein that bound hemagglutinin in three places simultaneously instead of just one, to improve on nature’s avidity—the overall strength of binding. They theorized this would be possible because hemagglutinin forms regular trimers on the surface of the virus. First, the team used a computational strategy to design a protein that could bind one of hemagglutinin’s sialic acid receptor sites (Nat. Biotechnol. 2017, DOI: 10.1038/nbt.3907). Then they built a scaffold that could orient three of these hemagglutinin-binding proteins simultaneously on the surface of the virus. When they tested their design, the three-pronged weapon neutralized influenza in cell culture and protected mice from infection by the pathogen.

 
Chemical & Engineering News
ISSN 0009-2347
Copyright © American Chemical Society

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