Exploring the Sciences

Unlocking the Mystery

Searching for Keys to Prevent the Spread of Mosquito-Borne Diseases

There has never been a greater need to combat West Nile virus, yellow fever, dengue fever, and other constantly evolving mosquito-borne diseases. With more than 2 billion people at risk of infection with dengue virus, a further 600 million people at risk of yellow fever, and no currently available drug options, new treatments are desperately needed.

Australian-born UNC Professor Susan Keenan has spent more than a decade researching and developing compounds to help prevent the growth of flaviviruses, more commonly known as mosquito-borne viruses. Such viruses must replicate to grow; Dr. Keenan’s research team is identifying compounds that will inhibit such replication. The most widely-known flaviviruses are West Nile, yellow fever and dengue fever. The West Nile Virus entered the United States in 1999, and the threat of certain other mosquito-borne diseases entering the southern United States grows as the world’s climate changes.

exploringDr. Keenan summarizes the need for her research with a sense of urgency. “These diseases are killers, and there are really no drugs to combat them,” she said. Dr. Keenan recently received a $1.4 million grant from the Rocky Mountain Regional Center of Excellence, funded by the National Institutes of Health, for her collaborative work with a colleague at Colorado State University. Through their unified approach, which combines computational modeling tools with molecular biology and pharmacology, the team members have discovered compounds that will bind to a flavivirus enzyme and prevent the viruses from replicating. This discovery comes after testing more than 300,000 compounds for antiviral activities. Another grant is allowing the team to test another 300,000 compounds in hopes of discovering even more disease-preventing compounds. The researchers have initiated live-virus studies with the long-term goal of developing the small molecules into drugs that would help combat mosquito-borne diseases.

mosquito“We are currently working on identifying the small molecules that can prevent these proteins from functioning correctly,” Dr. Keenan said, explaining her computational drug design approach. “We then use the computational tools to predict the activity of the molecule and then test the compounds that we believe are most likely to succeed against the protein target — it is rather like finding a key that can fit a particular lock.”

Dr. Keenan’s research team also includes undergraduate and graduate students at UNC. These students have an opportunity for hands-on research experiences in the laboratory, which is a huge benefit of a UNC education. Students gain technical skills, substantive knowledge of biology, and inspiration from being part of a cutting-edge research program.

Of course, the quest continues. “There is a long road to go,” Dr. Keenan said.

Bringing a new drug to market for any of these diseases will be a challenging endeavor since most people affected by these diseases live in poorer areas of the world, and the cost of developing a single drug generally exceeds $15 million. Additionally, the viruses regularly mutate and become resistant to drugs, making the research on flaviviruses an ongoing process. Dr. Keenan optimistically expects new drugs and targets to be developed in about five to 10 years.