Drug development advanced by USF research

Three USF scientists are working to develop a new method of drug development called Target Guided Synthesis (TGS), potentially leading to more effective treatment of influenza as well as other viruses.

According to the Centers for Disease Control and Prevention, 5 to 20 percent of Americans contract the flu virus every year, resulting in 200,000 hospitalizations and 36,000 deaths. The parties who are most susceptible to flu complications include young children, pregnant women, the elderly and those who suffer from chronic health conditions.

The research team – comprised of Roman Manetsch, Edwin Rivera-Otero, and Alberto van Olphen – uniquely combines the fields of organic chemistry, nuclear magnetic resonance and microbiology and hopes to test the efficacy of TGS. These tests could lead to the discovery of better flu drugs.

Manetsch, an assistant professor of chemistry, described TGS as a novel method of drug discovery, adding that the research team was in the stage of determining whether TGS does, in fact, work. If TGS proves effective, the process of drug discovery may become both less expensive and less time consuming.

“Before, drug discovery was kind of a two-step process, involving both the preparation of compounds and the testing of compounds,” Manetsch said.

In contrast, TGS is a one-step process, combining the preparation and testing of compounds in one step.

“We actually take the proteins and then dump in the fragments together, and then we mix it,” Manetsch said. “Then the protein actually picks the fragments which are the best, combines it together with a bigger molecule, and basically, you can say the protein is doing suicide. In the other case, you give something and then the protein actually has nothing to do, it just sees if it binds or not. But here, the protein is actually generating the compound which is the most active one.”

The addition of influenza protein to the testing solution actually induces the binding of compounds to one another. The product generated by this reaction thus becomes the candidate for a potential drug.

Van Olphen cautioned that this process does not always yield potential drugs.

“If you combine one compound from library A and one compound from library B and you don’t get a new compound, it means that the protein is not able to help make this new compound,” van Olphen said. “You will not always have a compound formed. Many times, these two will not bind with the protein. The protein will not be able to trigger it.”

Rivera, an associate professor of chemistry who is an expert in nuclear magnetic resonance, said the team decided to use the resonance technique in order to “screen” the compounds produced by TGS.

“It’s an analytical technique that we use for trying to determine how the compounds that are produced by TGS interact, or tell us how it binds, tell us whether it binds or not, and it also tells us if it binds and how tightly it binds to the target,” Rivera said.According to Rivera, tightness is key.

“The tighter it binds,” he said, “it’s more likely that this Target Guided product is to succeed as a drug.”

After the compound is selected through TGS and screened by nuclear magnetic resonance, the compound eventually makes its way to van Olphen – a veterinarian and microbiologist – who tests the compound as a drug.

“If we see that these compounds are able to reduce the growth of the virus to an acceptable level, then we can try to go to the next step and test it in animal models,” van Olphen said. “And then eventually, if all that goes great, then we may have a lead compound and we can try to look into more advanced studies and Phase 1, Phase 2, Phase 3 of trials. But that will take many years.”

The team recently received $70,000 in grants to help fund research.

Upon meeting at the College of Public Health’s Synergy Social, van Olphen and Rivera realized their varying expertise would be conducive to advanced biomedical research.

“That Synergy Social was like speed dating,” van Olphen said. “We had two minutes to talk to each other, but we liked what we were talking about so we kept talking. We cheated the system, basically. And we stayed there for a while talking about opportunities. Of course, Roman and Edwin knew each other – that’s how I met Roman – so that helped us start working on the idea. We found a problem, tried to find a solution, and started (grant) writing from there.”

And though van Olphen credits the idea’s genesis to chance conversation, Rivera believes otherwise.

“Actually, come to think about it, it was the Latin food at La Cocina, the spicy food, that might have gotten us started,” Rivera said.