LAWRENCE — A University of Kansas researcher is at the center of two projects aimed at developing treatments for infectious diseases, including the SARS-CoV-2 virus that causes COVID-19.
Scott Lovell, director of KU’s Protein Structure & X-Ray Crystallography Lab, and three collaborators recently received a $3.7 million grant from the National Institutes of Health National Institute of Allergy & Infectious Diseases to develop an antiviral therapeutic treatment that could help people who have contracted SARS-CoV-2.
The project involves principal investigators Kyeong-Ok “KC” Chang, a virologist at the Kansas State University College of Veterinary Medicine; William Groutas, a medicinal chemist at Wichita State University; and Stanley Perlman, a professor of microbiology and immunology at the University of Iowa.
The group began collaborating more than a decade ago to develop inhibitors that reduce or interfere with the activity of a viral protein, or main protease, found in both human and animal viruses, including noroviruses and coronaviruses.
“We were already working on an NIAID-funded project to develop inhibitors of the MERS coronavirus,” Lovell said, “so it made sense to leverage that expertise against the new SARS-CoV-2 virus.”
Lovell is the structural biologist for the group. His lab uses a technique called X-ray crystallography to determine the three-dimensional structure of a protein, which provides insight into protein function and guides drug development by providing a picture of the protein and drug interactions.
In the structure-determination process, the lab prepares a synthetic version of a protein to grow crystals and collect X-ray diffraction data that are used to determine the three-dimensional structure of the protein.
“Drug discovery is always a team effort,” Lovell said. “We have virologists and medicinal chemists who develop and study the effectiveness of the inhibitors against a specific viral protein named the main protease, which plays an important role in the propagation of the virus. As a structural biologist, my job is to figure out how those inhibitors bind to the protease at the atomic level. Having this information enables us to tailor-make more effective inhibitors using what is termed a structure-based approach.”
Lovell’s lab also recently began another project managing the protein crystallography work for the Seattle Structural Genomics Center for Infectious Disease, which is one of only two structural genomics centers in the country aimed at the structure determination of proteins from infectious organisms.
SSGCID’s goal is to determine the structures of proteins that play a role in bacterial or viral pathogenesis, or the process by which an infection leads to disease. SSGCID determines 70 to 100 protein structures each year and deposits them in databases that are publicly available to researchers. This resource provides an archive of protein structures that researchers worldwide can access to determine their potential as targets for the development of therapeutic drug treatments for both human and animal diseases.
“This work by Dr. Lovell and his collaborators is extremely significant in the effort to control the COVID-19 pandemic and the threat posed by infectious disease worldwide,” said Erik Lundquist, associate vice chancellor for research and professor of molecular biosciences. “These projects highlight the excellence and international reputation of Dr. Lovell in structural biology of infectious diseases. The critical expertise and work done in KU core labs has enabled projects such as these to have global impact.”
Top image: Three-dimensional rendering of the SARS-CoV-2 virus. Credit: iStock/BlackJack3D.
Bottom image: The X-ray crystallography technique determines the 3-dimensional structure of a protein.