MAY 24, 2017 1:34 PM PDT

Cancer Drug Indirectly Reduces Influenza Viral Load

WRITTEN BY: Kara Marker

Vaccines to prevent influenza infection have to change and adapt every year to the ever-evolving virus, and even current flu medications are becoming less effective as the virus learns to become resistant to specific antiviral attacks. However, there may be an easier approach to targeting flu viruses, by way of an indirect “back road” to take the virus by surprise.

 Corresponding author Paul Thomas, Ph.D., an associate member of the St. Jude Department of Immunology, and Heather Smallwood, Ph.D., of the University of Tennessee Health Science Center in Memphis. Credit: St. Jude Children's Research Hospital / Peter Barta

From St. Jude Children’s Research Hospital, scientists from a new study investigated the interaction between flu infection and the changes in lung epithelial cell metabolism. Early on, researchers suspected that metabolism could be a new potential target for anti-flu development.

Lung epithelial cells are very commonly targeted by flu as a viral replication site, in part because these cells have access to glucose and glutamine, which viruses can use for producing more viruses. In their study, researchers found that flu viruses can alter cell metabolism to increase their dependence on glucose and glutamine. They compared metabolism rates in the lungs of 20 immunocompromised pediatric cancer patients with respiratory infections compared to lungs of patients without infections. As confirmed in PET scan results, there is indeed a significant increase in glucose metabolism in virally-infected lung epithelial cells.

Next, researchers tested nearly 80 molecules and drugs, all of which targeted cell metabolism in some way. With the connection between metabolic activity and flu infection clearly demonstrated, they were now interested in identifying the best candidate for targeting that connection.

"By focusing on changing how infected cells respond to the resulting metabolic stress rather than targeting a component of the virus itself, there is less risk that the virus will become resistant to the drugs," explained Paul Thomas, PhD, from St. Jude.

A cancer drug called BEZ235 was one of several drugs identified to block a flu-related metabolic pathway. BEZ235 proved capable of both reversing infection-induced metabolic changes as well as limited the production of new flu viruses. In a mice model of flu infection, BEZ235 reduced respiratory infection symptoms and improved overall mice survival.

"This approach works by reducing viral replication, which suggests there might be a treatment window that lasts several days in which drugs could be used to reduce the infection and risk of complications," Thomas said.

BEZ235 is currently being tested as a cancer drug, now in clinical trials for the treatment of solid tumors. The experimental drug works by inhibiting two metabolic pathways - PI3K and mTOR - thereby inhibiting “unchecked cell division” that is all-too associated with cancer growth.

Tumor cells are similar to virally-infected cells in that they are both metabolically active. In the study, researchers showed that flu infections are similarly associated with increased PI3K and mTOR pathway activity. So, because BEZ235 inhibits PI3K and mTOR activity, BEZ235 can reduce viral load similarly to how it prevents unchecked cell division to suppress cancer growth. Specifically, BEZ235 suppresses virally-infected cells, preventing from using glucose and glutamine to produce more flu viruses.

In addition to the challenge of developing relevant vaccines every year and preventing flu from becoming resistant to antiviral drugs, the problem with flu is also the serious complications that are especially common and dangerous for high-risk patients: young and old, obese, chronically ill, immunocompromised. Plus, flu isn’t the only respiratory virus with serious repercussions for these people. With that in mind, researchers from St. Jude plan on continuing their study of BEZ235 and similar drugs in the context of flu but also other troublesome respiratory viruses.

The present study was published in the journal Cell Reports.

Source: St. Jude Children’s Research Hospital

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog:
You May Also Like
JAN 28, 2020
Clinical & Molecular DX
JAN 28, 2020
Protein complex discovered as first biomarker of PTSD
  Researchers at the Centre for Addiction and Mental Health (CAMH) and the Canadian Institutes of Health Research (CIHR) have identified a potential d...
JAN 29, 2020
JAN 29, 2020
Eating Eggs Everyday Not Linked to Heart Disease
The common controversy over whether eating eggs is bad for heart health may finally have been dissolved thanks to new findings by scientists at McMaster Un...
FEB 03, 2020
Genetics & Genomics
FEB 03, 2020
Advances in Genetics From the GenomeAsia 100K Project
Scientists are taking note of the lack of diversity in genetics, and some are trying to fix the problem, which affects everyone....
FEB 21, 2020
Health & Medicine
FEB 21, 2020
Should You Really be Scared of the Coronavirus?
As of February 21st, the death toll for coronavirus reached 2,250, 55,707 currently infected, of which 12,066 (22%) are in a serious or critical condition....
FEB 25, 2020
Cell & Molecular Biology
FEB 25, 2020
Relieving Preeclampsia With an Antioxidant Found in Mushrooms
Preeclampsia usually arises after 20 weeks of pregnancy in women that typically have normal blood pressure. It can be fatal to the mother and baby if left untreated....
FEB 25, 2020
FEB 25, 2020
Simple Blood Test May Prevent Deaths from Heart Attack
Cardiovascular disease is responsible for almost 18 million deaths every year, making it the top killing-disease in the world. Now, researchers at Newcastl...
Loading Comments...