OU College of Pharmacy Researcher Earns $2 Million Grant to Study Innovative Method of Controlling Viruses

OKLAHOMA CITY — As COVID-19 has demonstrated, viruses can emerge at any time and wreak havoc across the globe. Because many viruses mutate quickly, there are very few drugs to treat them, nor are there vaccines in many cases. What if there were a way to prevent a virus from hijacking the human protein it needs to replicate?

That is the focus of University of Oklahoma College of Pharmacy researcher Anthony Burgett, Ph.D. For a number of years, Burgett has been studying new targets for drug development, including for antiviral drugs, but the current pandemic has illuminated the importance of his research. He recently received a $2 million grant from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, to investigate a new approach for antiviral drug development.
Burgett’s research is unique in that he is not using a drug to target the virus itself — he is targeting a human protein that viruses need to replicate.

“For the most part, antiviral drug development for the many untreatable RNA viruses has attempted to target one viral protein found in one virus,” he said. “Therefore, these drugs likely will only be effective against one or a few known viruses. And, because of the high rate of mutation in these viruses, an antiviral drug targeting a viral protein is not likely to work for very long before drug-resistant viruses develop. In our research, we found a protein in human cells that many different kinds of viruses need in order to replicate. Our approach is to create a drug that prevents the viruses from using this human protein to replicate, which may be an effective therapeutic strategy not just for one virus, but for many different viruses.”

The protein he is studying is called oxysterol-binding protein (OSBP), which viruses “hijack” and use to replicate once they have infected someone. Several types of viruses are known to use OSBP, including hepatitis, Zika, Dengue Fever, several types of common cold viruses, and coronaviruses. Burgett and his research group made a drug-like molecule that binds to OSBP, blocking the viral hijacking and possibly sounding an alarm to other cells to turn on their antiviral defenses.

“Targeting the OSBP protein with a drug would potentially treat ongoing viral infections, but could prevent viral infections as well,” Burgett said. “And, since the OSBP protein is required for many different viruses, an OSBP-targeting drug would offer the possibility of making a person resistant to infection by many different viruses that have yet to emerge. That’s the advantage of targeting a human protein required by the virus for replication – our approach might work against viruses that we don’t even know about yet.”

As devastating as COVID-19 has been, it likely will not be the last time that a viral pandemic affects humanity, Burgett said. Aside from SARS-CoV-2, the novel virus that causes COVID-19, there are plenty of viruses already circulating that have the potential to transform into something more serious. For example, researchers for years have known about a virus called enterovirus D68, which caused very few infections for decades. But around 2014, it changed and caused millions of respiratory infections and hospitalized thousands of children, particularly those with asthma. Among those children, a few hundred were paralyzed because the virus caused permanent nerve damage.

“While the rate of paralysis was very small, that virus tomorrow could begin causing paralysis in many more children, and we would not have any existing therapeutic treatments,” he said. “This virus is one example of the current risk of viruses suddenly becoming public health emergencies and why developing antiviral treatments against numerous viruses is so important for human health.”
Research reported in this news release is supported by the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, under the award number 1R01AI154274-01A1. The grant also supports the work of Burgett’s collaborator, Earl Blewett, Ph.D., at the Oklahoma State University Center for Health Sciences. The project has also received funding from the Oklahoma Center for the Advancement of Science and Technology, the Barnes Family Foundation in Tulsa, and will be supported going forward by an equipment grant from the Presbyterian Health Foundation in Oklahoma City.

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