UTHSC Drug Discovery

Researcher works in the UTHSC COVID-19 Lab. Image courtesy of UTHSC/Natalie Brewer

A University of Tennessee Health Science Center (UTHSC) virologist and University of Tennessee Foundation (UTFI) fundraiser are working hard to further the holistic process of drug discovery in the fight against COVID-19 through innovative research and industry partnerships.

Michael Whitt

Michael Whitt is the associate dean and chair of the Department of Medical Education in the UTHSC College of Medicine and a professor in the Department of Microbiology, Immunology and Biochemistry. His research focuses on understanding the requirements for the replication and assembly of the enveloped, nonsegmented negative-stranded RNA virus called vesicular stomatitis virus (VSV). VSV is a non-human pathogen that features a broad host range and grows well in cell culture.

In the mid-1990s, Michael developed and patented a reverse genetics system for generating pseudotyped viruses with VSV that allows researchers to study highly pathogenic viruses like Ebola safely under standard biosafety level 2  laboratory containment measures. In the years since this innovation, Michael has primarily worked on developing VSV as an oncolytic virus, which infects and kills cancerous cells without harming normal cells. However, when the pandemic hit, Michael and a team of researchers began using his unique pseudotyping system to develop reagents to determine if people present neutralizing antibodies after exposure to the virus.

“We have a real opportunity to make a difference during this pandemic,” Michael said. “If we can help people get over the curve and provide reliable information that helps determine if it’s okay to go back to work or not, I think that would be great.”

 

His research aims to answer the question: After someone is infected with the virus, do they have antibodies that can protect them from subsequent infection? He is working in partnership with UTRF and other UTHSC researchers, along with companies and universities around the world, to leverage his system to enable rapid screening for these neutralizing antibodies.

“The system results in the assembly of the SARS-CoV-2 spike protein into a modified VSV, allowing researchers to work at a lower biosafety level than they would when working with the live SARS-CoV-2 virus,” Michael commented. “Additionally, the readout only takes around 15 hours, which makes the screening process faster, safer, and simpler.”

Greg Harris

While Michael and his colleagues fervently work on therapeutics and testing, Greg Harris pursues engaging potential industry partners. As a senior director of development with UTFI, Greg builds relationships with research funders to secure philanthropy for UTHSC’s Office of Research priorities, such as research labs. One such lab is the Regional Biocontainment Lab (RBL), directed by Colleen Jonsson. The RBL is currently conducting research on the COVID-19 virus to find a vaccine solution. Greg is in active discussions with several foundations and companies about providing philanthropic support for the COVID-19 research.

In addition to touting the talent and expertise of Colleen and her team, Greg is promoting a UTHSC advantage–the vertical stack or vertical platform. The vertical platform approach refers to the comprehensive nature of drug discovery efforts that can be conducted through the UTHSC system.

Greg explains, “We have most of the process at our institution: live virus testing at RBL, clinical studies through the Clinical Trials Network of Tennessee (CTN2), and product development at the Plough Center for Sterile Drug Delivery Solutions. In addition, the RBL can partner with ORNL to conduct computational and virtual screening on the Summit supercomputer. Almost everything can be achieved through our network.”

The RBL team is working on several options. As the ORNL Summit supercomputer simulates and identifies effective inhibitors of COVID-19, the RBL tests the prospective molecules. The RBL is also working to extract and sequence viral RNA, allowing scientists to study differences in COVID spread and severity across different strains of the SARS-CoV-2 virus. To date, Greg has helped secure two gifts to support the RBL’s work, with several additional requests pending. Greg says current conversations regard positioning the RBL for the next stage. Much of the current COVID-19 research is focused on repurposing existing human drugs. If a solution is not found, institutions will turn their focus on animal drugs and live virus screenings. The RBL has built a pipeline of potential COVID-19 candidates consisting of FDA approved animal drugs and unique small molecule collections not commercially available.

Before the pandemic hit, neither Michael nor Greg envisioned they would work on these projects, yet both are committed to using their respective skills and expertise to join the ranks of individuals and organizations around the world fighting the virus.

“We are working to save lives and help humankind,” Greg said. “How wonderful would it be if UTHSC found a solution for this pandemic and saved thousands of lives?”

“UTHSC has marshalled its collective expertise to combat this pandemic in so many ways,” Richard Magid, vice president of UTRF, said. “UTRF is proud to support researchers like Michael and visionaries like Greg to use the tools of research and industry partnerships to understand and solve COVID-19.”