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Molecule discovery may help lower influenza-related deaths

Last year’s flu season produced higher rates of hospitalization and more influenza-related deaths than recent years, according to the Centers for Disease Control and Prevention.

The discovery of a new molecule by a team of Rutgers and University of Rochester researchers, though, may help lower those numbers within the next decade.

The molecule targets a protein in the influenza A virus, stopping the flu virus from replicating in cell cultures, said Joseph Bauman, a research associate at the Center of Advanced Biotechnology and Medicine.

According to the CDC, influenza A is responsible for the swine and bird flus. It was the dominant flu in the U.S. between 2012 and 2013.

The development of resistance to the drugs is always an issue, according to the center, despite the fact that four drugs combatting influenza A currently exist on the market.

Last flu season, the center reported the outbreak of a new variant of the virus, H3N2. The new virus infected four people from the state of Indiana in one week.

But the new molecule avoids the resistance to the popular drug Tamiflu, Bauman said. It will provide future victims with a potential alternative for treatment.

The team’s work began with high-resolution images of the targeted protein produced by Bauman and Kalyan Das, a research professor at the Center of Advanced Biotechnology and Medicine. Bauman said he and post-doctoral fellow Dishaben Patel then used fragment screening to develop the molecule.

Bauman said he and Patel screened 800 molecular fragments to design the molecule.

Once they developed the molecule’s structure, Bauman said the team collaborated with Edmond LaVoie, chair of medicinal chemistry in the Ernest Mario School of Pharmacy, to increase the molecule’s potency.

With LaVoie’s help, the team increased the potency by over 1000 times, Patel said.

“It’s a lot like legos,” Patel said. “We are basically building the molecule.”

Once the molecule was designed, Patel said a University of Rochester virologist Luis Martinez-Sobrido tested and found the molecule’s antiviral activity on the cell cultures.

Patel said the team published their discovery in the American Chemical Society’s Chemical Biology journal last August.

Bauman said the team now prepares for testing the molecule’s antiviral activity on animals.

He said within the next two to three years, the molecule would be ready for clinical trials.

“Usually, drugs take five to seven years to reach clinical testing. Our method is super efficient,” he said.

The team’s method has roots in the structural-based drug design used to create Edurant, an anti-HIV drug developed by Edward Arnold, a professor in the Department of Chemistry and Chemical Biology, roughly 15 years ago, Bauman said.

In an interview with Rutgers Today, Arnold said universities and pharmaceutical companies attempted the approach almost 20 years ago, but at the time, the technology could not produce high-resolution images of the targeted influenza protein.

Still, he said the pharmaceutical company Merck used the method to develop a successful anti-HIVs drug.

He said while the team is in an early stage of production, the class of molecules they have discovered has all the right characteristics for developing an effective drug.

“We’re optimistic,” he said.

Bauman said now, the team only takes a single day to determine the structure of the molecule they need.

“It’s a very logical, fast approach,” he said.

One of the team’s bigger issues is funding, he said. Most of the team’s previous funding came from Rutgers, but it has little left.

In hopes of securing funding faster, Bauman, Arnold, LaVoie and Gregory Mario, the CEO of TAXIS Pharmaceuticals, have started a company dedicated to anti-flu research.

He said the start-up company, Prodaptics Pharmaceuticals, is still a virtual company, but it will hopefully help bring the drug to the market within the next six to eight years.

The idea of funding a project this way is recent, Bauman said, but not unheard of. Research groups at universities are becoming more resourceful and independent of industry.

Patel said as financial drawbacks of working in academia are disappearing, business incentives for conducting research are on the rise.

“Academia is finally reaching the level of [the] industry,” she said.

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