The University of Alabama at Birmingham (UAB) School of Medicine is working with top scientists from across the country to create a national research consortium focused on the discovery of new and better drug therapies to treat emerging or re-emerging viral infections that pose global health threats, but for which there are limited or no treatment options.
UAB will lead in the establishment of the Antiviral Drug Discovery and Development Center (AD3C), funded by an up to $35 million, five-year grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).
The Center will focus on developing drugs against four RNA virus families: influenza, flaviviruses, coronaviruses and alphaviruses—infections causing diseases including West Nile, SARS, chikungunya and dengue. Researchers will work to target and inhibit specific enzymes essential for viral replication and expression of viral genes, with AD3C providing an infrastructure to accelerate the development of new potential drugs from the lab towards the clinic.
UAB will coordinate the research with top virologists across the country already working with these viral agents. Investigators Jay Nelson, Ph.D. at Oregon Health and Science University (OHSU) and Michael Diamond, M.D., Ph.D., at Washington University will focus on flaviviruses, which include yellow fever, West Nile virus and dengue; Mark Denison, M.D., at Vanderbilt University and Ralph Baric, Ph.D. at the University of North Carolina (UNC) at Chapel Hill, will focus on coronaviruses, which includes SARS; Daniel Streblow, Ph.D., at OHSU and Mark Heise, Ph.D., at UNC, will work on alphaviruses, which include chikungunya and Venezuelan equine encephalitis. Richard J. Whitley, M.D., and other scientists at UAB will be studying compounds active against influenza with Ghalib Alkhatib, Ph.D., and James Noah, Ph.D., at Birmingham’s Southern Research. Whitley, a distinguished professor and vice chair in the UAB Department of Pediatrics and renowned expert in antiviral treatments will serve as the principal investigator and program director of the AD3C.
In 2008, Southern Research and UAB created the Alabama Drug Discovery Alliance to facilitate the discovery and development of new drug therapies. “UAB and Southern Research, over the last five years, have spent a lot of time, money, and energy developing the Alabama Drug Discovery Alliance. Having done that, being awarded this grant shows how that investment can pay off,” says Whitley. “These families of viruses are of the highest priority for the U.S. government. They represent both biologic threats and unmet medical needs,” says Whitley. He says the global burden of these diseases is enormous, with West Nile virus and influenza routinely infecting U.S. citizens. “We will also strive to develop therapies for emerging infections such as coronaviruses, dengue and chikungunya, which pose risks for traveling U.S. citizens or could be imported into the country.”
The AD3C comprises three main cores: an administrative core, housed at UAB, will deal with day-to-day operations of the Center and serve as the hub for the Executive Committee and External Scientific Advisory Board that will monitor the research progress and provide expertise and a frequent high-level review of AD3C. A screening core at Southern Research will develop and perform high-throughput screening assays for compounds that inhibit viral processes that are essential to the viability of the organism, Whitley says.
A medicinal chemistry and lead development core, also at Southern Research, will provide chemistry capabilities to manipulate and optimize compounds found to work in screening, and make them more ‘drug-like’, with the goal of creating new potential therapies.
“The best outcome of this research would be that, over the next five years, we’re able to develop drugs that can treat humans who have influenza, dengue fever, West Nile virus, SARS coronavirus, MERS coronavirus and chikungunya,” Whitley says. “This team of investigators from across the country and their respective institutions represents terrific intellectual talent to address these challenges.”