12/09/2021
Researchers to Study if Non-Coding SARS-CoV-2 Genetic Material Can Offer Insights into New COVID-19 Therapies
The National Institutes of Health has awarded Paul Fox, PhD, and colleagues a three-year, $1.2 million grant to study mechanisms of SARS-CoV-2 (the virus that causes COVID-19) gene regulation and investigate novel targets for new antiviral therapies to treat or prevent COVID-19. The project will be a collaboration between Dr. Fox’s lab and researchers from Cleveland Clinic’s Florida Research & Innovation Center.
“While the development of COVID-19 vaccines was greatly accelerated, the field has not been as quick to develop antiviral therapies,” said Dr. Fox, who is staff in the Department of Cardiovascular & Metabolic Sciences. “There are many people, however, that may not be as well protected by vaccines and who would benefit from antiviral treatment, underscoring the need to advance this area of study and drug development.”
With support of this new grant, Dr. Fox and his collaborators—including Debjit Khan, PhD; Fulvia Terenzi, PhD; Michaela Gack, PhD; and Guanqun Liu, PhD—will turn their attention to the non-coding regions of SARS-CoV-2 genetic material, including RNA and subgenomic messenger RNA. As implied by the name, non-coding RNA does not encode proteins. However, these regions of genetic material are still very important. For example, some types of non-coding RNA can direct whether genes are turned on or off and some have been implicated in driving disease processes.
“Our goal is to ascertain if there are elements within these non-coding regions of viral genetic material that can be targeted with antiviral drugs,” proposed Dr. Fox, who is also the Robert Canova Endowed Chair in Inflammation Research.
Interestingly, Dr. Fox’s team has already identified that a pro-inflammatory molecule called IFN-γ and insulin, an obesity-related hormone, increase the binding of specific proteins to a non-coding region of SARS-CoV-2 RNA.
“Obesity is a well-recognized risk factor for COVID-19 infection and disease severity,” said Dr. Fox. “This fact highlights the need to develop antiviral drugs for populations that may not be optimally protected by vaccines and existing therapeutics. But it also, when coupled with our findings about insulin, gives us an interesting place to start our investigations into new drug targets.”
This study is supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Drs. Khan and Terenzi are both members of Dr. Fox’s lab. Dr. Gack is the scientific director of the Florida Research & Innovation Center. Dr. Liu is a member of her lab.
