Researchers Win Funding for New Therapies for Gastroenteritis

CINCINNATI—University of Cincinnati (UC) researchers have received National Institutes of Health (NIH) funding to develop new therapies for gastroenteritis, a common cause of illness and death worldwide.

Jarek Meller, PhD, an associate professor in the UC Department of Environmental Health’s Division of Epidemiology and Biostatistics, is the principal investigator on a project that received a two-year award of $394,257 from the NIH’s National Institute of Allergy and Infectious Diseases.

Meller will work with Jason Jiang, PhD, and Ming Tan, PhD, professor and assistant professor, respectively, in the UC Department of Pediatrics. Both are based in the Division of Infectious Diseases at Cincinnati Children’s Hospital Medical Center and have a long-standing collaboration with Meller, whose research is focused on developing and applying computational approaches for data mining, analysis and knowledge extraction from biomedical data. 

The research project will focus on strategies to prevent the human norovirus (NV) infection, the most common cause of acute gastroenteritis (also known as food poisoning or stomach flu) in the United States. According to the U.S. Centers for Disease Control and Prevention, norovirus causes 19 million to 21 million illnesses annually and contributes to between 56,000 and 71,000 hospitalizations and 570 to 800 deaths.

Common symptoms of norovirus illness include stomach pain, nausea, vomiting and diarrhea, along with fever, headaches and body aches. It is not related to the flu, which is a respiratory illness caused by influenza virus. There is no specific medicine to treat it; as a viral (not bacterial) infection, it cannot be successfully treated with antibiotics.

Meller’s team intends to use in silico (computer-aided) and in vitro screening to identify small molecules that can effectively destabilize or disrupt the assembly of the NV capsid, the protein shell that surrounds the virus. They’ll be looking for "hot spots” within the capsid, with an eye toward identifying small molecules that would target such sites and effectively block NV-caused gastroenteritis.

These molecules, called allosteric inhibitors, can disrupt capsid assembly by targeting intermediate conformations of capsid proteins and protein-protein interaction interfaces within the capsid particles. 

"Targeting NV capsid represents a novel strategy that has been successfully applied to other viruses, including HIV, in recent years,” Meller says.

Meller notes that research could lead to medications that would be taken under specific circumstances when gastroenteritis is perceived as a threat; for example, when an outbreak occurs on a cruise ship or following a restaurant visit by a large group of family or friends who start exhibiting symptoms of gastroenteritis.

The project is currently underway and is scheduled to conclude July 31, 2015.