OHIO researchers returning to labs to research potential COVID-19 treatments

Ben Siegel/51��

Dr. Shiyong Wu meets with students in 2019.

Several 51�� researchers have received permission for an early return to their labs to conduct research on potential treatments for COVID-19.

While most on-campus research activity was paused under the state’s stay-at-home order, the university has allowed a limited amount of essential work to continue — with close attention to safety. Research related to the COVID-19 pandemic qualifies as essential, said Joseph Shields, vice president for research and creative activity.

“Given the serious and significant impact of COVID-19 on our world, 51�� has allowed some of its researchers to resume work in labs to join the global scientific fight against this virus. We also are helping our faculty identify and apply for new external funding opportunities for COVID-19 research,” Shields said.

In April, the University announced that Kelly McCall and Doug Goetz of the Heritage College of Osteopathic Medicine and Russ College of Engineering and Technology, respectively, had been awarded a $100,000 Fast Grant from Emergent Ventures, a fellowship and grant program at the Mercatus Center of George Mason University. The researchers are examining specific compounds that could have the potential to inhibit the “cytokine storms” that may lead to serious medical complications and death in individuals infected with the coronavirus.

“This summer we will test the GSK3 inhibitors in our cell culture models to evaluate the inhibitors’ possible use as COVID-19 therapeutics. If we find one or more have efficacy in these models, we will reach out to collaborators at other institutions to test these inhibitors using the virus and patient samples,” McCall and Goetz reported.

Three research labs in the Department of Chemistry and Biochemistry in the College of Arts and Sciences are using other funding sources and the expertise of their faculty, student and staff research teams to investigate other possible ways to combat COVID-19.

Professor Shiyong Wu, who serves as director of the Edison Biotechnology Institute, and his team are examining whether a particular bacterium could be used to neutralize the coronavirus. The parasitic bacterium protects people from infectious pathogens, he explained, and can survive in various microenvironments found within the human body. The Wu team will determine if they can embed the peptides that COVID-19 seeks to attach to in the human body within the bacterium. This could allow the bacterium to intercept the virus before it can spread further through the body.

“We know what coronavirus targets — we know the receptor it attacks on human cells,” he said.

The team — which includes graduate students, a postdoctoral fellow and staff scientists — will spend the summer months studying whether the concept works. If the idea shows promise, the researchers can ask an external lab to perform toxicology tests. Wu, who will use funds from the Konneker Research Endowment for the project, also has submitted a proposal to a funding program designed to support COVID-19 research.

Professor Eric Masson asked to return to his lab after reading about possible synergies between the COVID-19 virus and the Cucurbituril family of molecules that he has long studied. Cucurbiturils are hollow, pumpkin-shaped molecules that are of interest to scientists because of their potential applications, ranging from drug development to material science.

“A motif in one of the key proteins involved in coronavirus replication matches a motif that binds to our Cucurbituril-based systems. It was luck,” he said.

Masson’s team used modeling software to test how the shape of that coronavirus protein may interface with his Cucurbituril-based system, a pair of platinum complexes secured together by the large pumpkin-shaped macrocycle. It really fits “like a lock and a key,” he said, which gave the researchers encouragement that their system might bind to the protein and interrupt the replication of the virus.

Masson’s team now is heading back into the lab to conduct experiments to show how well their system can bind to a protein similar to the one produced by COVID-19.

While the new project draws on some existing expertise and skills of the team — which includes graduate students, a postdoctoral fellow and a visiting scholar — it also will allow them to branch out into new scientific techniques, Masson noted. Masson previously was awarded two grants from the National Science Foundation and two grants from the American Chemical Society Petroleum Research Fund to study some fundamental properties of the Cucurbituril family, and that has laid a solid foundation for the new COVID-19 experiments. Masson also will draw on Research Incentive funds and apply for additional grants.

A new COVID-19 research project led by Professor Jennifer Hines was inspired by an online tutorial she led for two Honors Tutorial College students earlier this spring. She received a grant from the Ohio Supercomputer Center to allow the students to use software to study how new drugs are developed — using the coronavirus as the example. After observing their initial results, she got permission to continue to use the center’s resources to conduct more targeted research on the subject.

“We will investigate whether existing, FDA-approved drugs can bind and disrupt an RNA structural element found in SARS-COV-2, the virus that causes COVID-19,” Hines said. “If so, these drugs potentially could be rapidly repurposed for the treatment of the disease. Other researchers have investigated drug repurposing for targeting viral proteins, but very few are looking at viral RNA.”

A team of graduate and undergraduate students, including the two HTC students involved in the spring tutorial, will plan and analyze experiments remotely. The graduate students will conduct the work in the lab.

In addition to studying FDA-approved drugs this summer, Hines hopes that her team also can design novel synthetic compounds that could help researchers develop a new drug that can target COVID-19’s viral RNA.

Each 51�� research team noted that it is strictly following University, state and federal guidelines for safety during the COVID-19 outbreak. While lab safety requires more than one individual to be present during experiments, the researchers are practicing social distancing in the lab, wearing protective gear and frequently washing hands and sanitizing. In addition, the faculty stressed that they are not working directly with the COVID-19 virus in these experiments.

“The health of our students is more important than the research output,” Masson said. “When I prepared this plan, I really took all the necessary precautions to reopen the lab in a safe manner.”

Any potential therapeutic treatment for COVID-19 will take time to develop — moving from proof-of-concept to efficacy and safety testing before it can be commercialized for public use. The 51�� Technology Transfer Office works closely with researchers to patent new technologies and identify companies that could take new products to market.

Although the 51�� teams are just beginning research on COVID-19, the researchers expressed a strong desire to use their scientific knowledge to contribute to efforts to restore global health.

“We are working very hard on this project despite the necessary restrictions and hope that our studies will contribute to the fight against this pandemic,” McCall and Goetz said.

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