OHIO researchers win grant to study treatment for possible fatal complications of COVID-19

Faculty researchers from Ohio University’s Heritage College of Osteopathic Medicine and Russ College of Engineering and Technology have received a $100,000 grant to investigate possible treatments for mitigating the severity of COVID-19.

Kelly McCall, Ph.D., and Douglas Goetz, Ph.D., will measure how effective a number of different chemical compounds are at preventing “cytokine storms,” a sometimes-fatal complication that can stem from COVID-19 infections.

The body responds to the presence of a pathogen by releasing a swarm of immune system proteins called cytokines to help fight off the virus or bacterium. If too many cytokines are released, a cytokine storm develops which can severely damage organs. This reaction is believed to be responsible for some of the deaths from COVID-19.

McCall is a professor in the Heritage College Department of Specialty Medicine and an investigator with its Diabetes Institute, and Goetz is a professor of chemical and biomolecular engineering in the Russ College.

Their award is a Fast Grant from Emergent Ventures, a fellowship and grant program at the Mercatus Center of George Mason University in Virginia. On April 7 the Center announced a grant program to provide funding for research on COVID-19. Reflecting the urgency of the worldwide search for ways to treat the pandemic, Goetz and McCall wrote the grant application in just three days, and it was approved within just a few days of its submission.

“This is exciting and welcome news,” said Ohio University President M. Duane Nellis, Ph.D. “The University has been eager to lend the expertise of our scientists to the urgent, cooperative global effort now underway to contain and treat COVID-19. We’re grateful to Emergent Ventures’ Fast Grants program for recognizing the merits of Dr. McCall and Dr. Goetz’s research proposal so quickly.”

According to Goetz and McCall, inhibiting the action of GSK-3 enzymes, highly active catalysts believed to play a role in producing cytokine storms, might help prevent the storms. A handful of GSK-3 inhibitors have been or are now being used in clinical trials; the researchers will be testing the effectiveness of five of these compounds.

“I’m extremely grateful to Emergent Ventures for creating the opportunity for scientists from all over the world to work toward combating this devastating pandemic,” Goetz said. “I’m also thankful for my longtime colleague Dr. McCall and the talented Russ College students and Heritage College scientists who have put us in an excellent position to make a contribution to this endeavor.”

McCall noted that the grant proposal stemmed from research she, Goetz and colleagues have been working on for years: studying how toll-like receptors, a class of proteins that play an important role in the immune system, are involved in producing cytokine storms. As part of this research, they have developed some compounds that are highly effective at inhibiting the action of an enzyme known as GSK-3.

“We realized that these GSK-3 inhibitors may act to block the cytokine storm that can be induced by pathogens such as viruses and bacteria,” McCall explained. Given the suspected role of cytokine storms in COVID-19 fatalities, Goetz and McCall realized that GSK-3 inhibitors might be used as a treatment.

They aim to test inhibitors already approved for safety, given how long it takes to get federal approval for a new drug for humans.

“Our hope is, if those are useful for COVID-19, then hopefully it will save people’s lives in the short term,” McCall said.  

In the aftermath of the 2003 SARS epidemic (a less pervasive coronavirus disease), researchers utilized the “spike protein” from the SARS virus and found that the protein itself can trigger an innate immune response which is germane to cytokine storms. McCall and Goetz plan to take a similar approach, introducing the COVID-19 virus’s spike protein to different types of cells, with and without the presence of an inhibitor, then comparing the levels of cytokines produced in each case. The spike protein projects from the surface of the virus and helps it attach itself to cells in a person’s body, making it a key factor in the virus’s ability to infect human cells.

Using the spike protein alone to trigger this response means the scientists will not need to have the virus present in their lab. Should they discover promising compounds, the team will partner with collaborators established through the Fast Grant network to test the compounds using SARS CoV-2 (the virus responsible for COVID-19) and patient samples.

“As soon as the growing threat from COVID-19 became apparent, our college mobilized its resources quickly to do everything we could to help, from reinforcing our state’s health care workforce to donating protective equipment,” said Ken Johnson, D.O., Heritage College executive dean and Ohio University chief medical affairs officer. “This grant from Emergent Ventures allows Drs. McCall and Goetz to build on their existing research and, we hope, contribute to relieving the suffering caused by this worldwide pandemic.”

Mei Wei, Ph.D., dean of the Russ College and Moss professor of engineering education, said, “I congratulate Drs. McCall and Goetz for receiving the Emergent Ventures’ Fast Grant. I am very pleased to see that the collaborative work between Russ College faculty and faculty of the Heritage College can contribute to the better understanding of GSK-3 inhibitors for COVID -19, thereby helping mitigate the pandemic.”