Scientists are taking a new approach in the fight against the flu. They have engineered a protein that acts to stop the virus from infecting cells, and while a lot more research is yet to be done, the new protein has been promising in tests done with cells in culture and animal models. The work, outlined in the video below, has been published in Nature Biotechnology.
Influenza is a public health threat, causing serious illness in anywhere from three to five million people in one year, an infection that is deadly to some 250,000 to 500,000 people, usually those with weak immune systems.
Vaccines are one way people can help prevent flu infection, but they are not effective against all strains and they sometimes don’t trigger enough of a response in some recipients. Drugs that act to fight the flu have traditionally been directed at proteins in the viral coat. Neuraminidase is one, but viruses have already started to build resistance to neuraminidase drugs. Another target on scientists’ radar is hemagglutinin (HA).
HA, a protein shaped like a mushroom, functions to aid the cell infection process. It begins by attaching its cap to three sugar molecules on the targeted cell individually. After binding, HA uses its stem like a hook to pull the virus close to the cell, after which it fuses and ejects the viral load into the cell.
David Baker, a computational biologist at the University of Washington in Seattle, led researchers in 2011 who synthesized a protein that binds to the stem portion of HA and could halt viral infection in cell culture models. The stem is often shielded by protein that puts it out the reach of drugs, however.
Baker’s team has now engineered proteins that target the exposed cap of HA instead.
The investigators tested copies of the protein that had been team immobilized nitrocellulose, a membrane that is like a kind of paper. After exposing it to various viral strains, it showed that it could attach to the virus without releasing it. “We call it flu glue, because it doesn’t let go,” Baker explained.
After trying out the protein in culture, the protein could prevent infection in the cells. It also stopped illness in mice when provided one day before or after exposure to virus.
The scientists note that this new protein is unlikely to become a medicine. One issue, explained Baker, is that the protein will not attach to flu strains that tend to sicken people. As such, any future drug be made up of a cocktail of proteins that attach to the HA cap or ones which act together with proteins that bind to the stem. Additionally, designer proteins have to be properly evaluated for safety, Crowe said; they are quite different from natural antibodies that halt HA. “The further you get away from a natural antibody, the less you can predict what will happen,” Crowe said.
This designer protein could one day be used in cheap diagnostic tests for the flu, like a pregnancy test, Baker said. It could also help doctors select the best medicine for flu treatment.
Sources: Science, Nature Biotechnology
