October 25, 2013
Food Additive May Prevent H7N9 From Infecting Host Cells
Lawrence LeBlond for redOrbit.com - Your Universe Online
As China continues to battle an outbreak of avian influenza A (H7N9), a team of researchers from the University of Illinois at Chicago College of Medicine are among those looking for ways to intervene and bring an end to a disease that has so far killed more than 20 percent of those it has infected.
The university team, led by Michael Caffrey, associate professor of biochemistry and molecular genetics at IUC, has found a common food additive that can block a strain of the avian influenza virus from infecting healthy cells. They are now reporting this new discovery in a published paper in the online journal PLoS ONE.
The compound, commonly used as a preservative, binds to a part of the virus that has never been targeted by antiviral drugs currently on the market. The research team said this discovery raises the hopes of developing a new effective drug that can take down a host of viruses that are known to out-survive anti-viral therapies.
"The recent H7N9 outbreak in China this past March had a mortality rate of more than 20 percent," said Caffrey. That strain, which is new, is already showing resistance to the majority of existing drugs used to treat it, he added.
If a preventative drug can be developed using this new compound, it could very well lead to saving countless lives that have been susceptible to drug-resistant viruses.
Preventing an outbreak that could lead to mass casualties would be difficult with the current arsenal, added Caffrey. "The need to develop new antiviral therapeutics now is crucial."
And “crucial” is the correct term, given that the 2013 H7N9 outbreak has so far sickened 137 people, and has left at least 45 dead. The World Health Organization on Thursday reported an additional laboratory-confirmed case of the virus, as notified by China’s National Health and Family Planning Commission (NHFPC).
The latest patient is a 67-year-old man from Zhejiang Province. He is known to have been in contact with live poultry, the known transmission route for this strain of the virus. He became ill on October 16 and was admitted to a local hospital on October 18. He was subsequently transferred to another facility on October 21 as his condition was deteriorating. He is currently in critical condition.
Cases such as this one may not need to be the norm if Caffrey and his associates have anything to say about it.
The additive that could potentially be used to treat such cases is called tert-butyl hydroquinone. It is an FDA-approved additive that has been found to stick to a specific region of the hemagglutinin molecule. This hemagglutinin molecule is a special protein that allows flu viruses to enter host cells via a receptor on the cell surface. If the molecule could be disabled, the virus would be locked out of the host cells, preventing an infection from occurring.
Caffrey and colleagues found that the additive "attaches to the Achilles' heel of the virus—a loop-shaped portion of hemagglutinin necessary for binding to cells, making cell infection impossible." The loop on the hemagglutinin molecule represents a new therapeutic target, since existing drugs do not go after it, he added.
"Any drugs that focus on the hemagglutinin loop would be totally novel to flu viruses, and so resistance, if developed, would still be a long way off," he said.
Early this spring, when the H7N9 flu virus first made its presence known in China, Caffrey and his team were looking at a totally different class of viruses that their additive could disable.
"Tert-butyl hydroquinone was known to have virus-blocking effects for H3 viruses," he said. "So when the H7N9 outbreak occurred, we thought we'd see if it had any effect on H7 viruses."
They were surprised to find that through utilizing a novel technique -- fusing hemagglutiniin of H7N9 to a less dangerous virus -- tert-butyl hydroquinone was able to prevent H7N9 from infecting human lung cells in the lab.
The research team is now looking for ways to enhance the additive’s ability to prevent infection. They suggest one way might be adding it to poultry feed. Keeping the virus from spreading in chickens would go a long way in reducing the likeliness of it making a move from birds to humans, noted Caffrey.
Interestingly, the researchers do not yet know if the food additive could be safely consumed in much higher doses than it is already approved for. That would likely be another factor in developing a preventative drug for H7N9, as well as other similar viruses.