$21 Million National Institutes of Health grant strengthens infectious disease capabilities in Wisconsin
Viruses without a preventative vaccine or treatment option pose a looming threat. But for viruses in this category that have already been weaponized and are recognized as human biothreats by the Centers for Disease Control and Prevention, it’s a race to find a cure.
For equine encephalitis viruses, or EEVs, this scenario is made more dire in that the viruses infect humans through the bite of an infected mosquito. With no human FDA-approved drugs against these pathogens, the human population is at risk. EEV infection in people can manifest as relatively mild flu-like symptoms or can progress to neurological impairment, seizures, or death. The most severe of the three EEVs, Eastern equine encephalitis virus, has been diagnosed in at least 20 states — including Wisconsin — and has a mortality rate of greater than 50 percent.
“We’ve made a breakthrough in creating new small molecules that penetrate into the brain where the virus resides and interfere with viral replication to stop EEV,” said Jennifer E. Golden, PhD, assistant professor of pharmaceutical sciences and associate director of the Medicinal Chemistry Center at the University of Wisconsin–Madison School of Pharmacy.
In Golden’s study published in Antiviral Research this month, Golden and her collaborators show that all of the mice treated with one compound developed in the Golden Lab at the School of Pharmacy survived when exposed to a lethal EEV.
“The UW–Madison School of Pharmacy is the engine of this important drug discovery work right here in Wisconsin.” –Steven Swanson
“Remarkably, we also show that delaying treatment for 48 hours to mice that are already infected still results in 90 percent survival. Now we’re working to better resolve the mechanism behind the antiviral effects that we observe, along with compound characteristics that must be understood, before a compound can be developed into a drug,” said Golden.
Golden is one of the three principal investigators on a multidisciplinary research team whose work is funded by a new, five-year $21 million award from the National Institutes of Health (NIH). The NIH funding establishes a new Center of Excellence for Encephalitic Alphavirus Therapeutics (CEEATR), which will support the preclinical development of small molecules to treat EEVs.
“The goal of this new grant is to develop a safe and effective broad-spectrum antiviral through preclinical assessment to clinical candidacy for FDA review before human clinical trials,” said Golden.
One of the most difficult tasks for Golden and her research team is balancing features that make a molecule effective against EEVs but also safe for a patient. Pioneering chemistry that modifies the molecular structure to afford a compound that is both safe and effective takes persistence, experience, and a coordinated effort between chemistry and biology.
“The UW–Madison School of Pharmacy is the engine of this important drug discovery work right here in Wisconsin, having the full capabilities to identify, design, and develop novel compounds that will improve human health,” said Steven Swanson, dean of the School of Pharmacy. “It’s no small feat to create new chemistry with this kind of complexity.”
Golden’s virology research collaborators in the new Center of Excellence for Encephalitic Alphavirus Therapeutics (CEEATR) include Colleen Jonsson, PhD, at the University of Tennessee Health Science Center, and Donghoon Chung, PhD, at the University of Louisville Center for Predictive Medicine. Golden, a medicinal chemist, is leading the design and synthesis of the antiviral compounds. Jonsson is implementing the animal efficacy and viral resistance studies, and Chung provides cellular and biochemical assays to evaluate cellular activity and determine how the compounds target the viruses.
With the establishment of the CEEATR, the interdisciplinary research team has assembled a world-class team of scientists with exceptional cross-disciplinary drug development and scientific expertise to optimize antiviral compounds that are effective for emerging EEV viruses.
Learn more about Dr. Golden’s research in the Golden Lab and the exciting work in drug discovery by the School’s Medicinal Chemistry Center.