A team of Temple scientists used a cluster of computers to study ways in which to fight the flu, and has found a way to stop the virus from replicating.
They used a simulation – which was part of a larger, multi-university study that was published in the December 2014 issue of the Journal of the American Chemical Society.
The computer cluster, known as the Owl’s Nest, resides in the TECH Center on Main Campus. “It is 2,000 times more powerful than your ordinary laptop,” said Dr. Michael Klein, director of Temple’s Institute for Computational Molecular Science and a co-author of the study.
Klein, who is also the dean of the College of Science and Technology, was quick to point out that the supercomputer is a means to an end.
“What’s more amazing is that we can study real-world problems, that we can have an impact on biomedical research,” he said.
He and his team focused on one such problem: the flu virus. Each flu season, the virus mutates slightly, and more and more flu strains become resistant to existing antiviral drugs. Amantadine, the first anti-flu drug, was introduced in 1999, but became ineffective against most flu strains by 2006. Tamiflu, a newer anti-flu drug, is also becoming less effective each year.
“When Tamiflu stops working, we’ll be in trouble,” Klein said.
Members of the team at the University of California, San Francisco, tested several modified amantadine molecules against two viral strains. At the same time, Klein’s team simulated potential binding mechanisms for these molecules on the Owl’s Nest.
“We wanted to have a molecule that’s able to defeat at least two if not more variants of the virus,” said Dr. Eleonora Gianti, a co-author of the study.
“We’re keeping the virus off its game,” said Dr. Giacomo Fiorin, also a co-author of the study.
The flu virus can only replicate inside human cells. During an infection, it infiltrates human cells by disguising itself. Once inside the cell, a protein known as M2 tells the virus it has entered the cell and can then begin replicating and infecting other cells. When M2 malfunctions, the virus cannot “see” that it is inside the cell, and it won’t replicate, Fiorin said.
The team’s modified amantadine plugs M2 and prevents the virus from replicating.
More importantly, the modified amantadine binds to at least two flu strains, one of which is resistant to amantadine.
“Here, the novel twist was to devise a molecule that would bind in one configuration and then the molecule can bind another way,” Klein said.
The team proved the modified amantadine works in the lab, but the compound is not yet ready for the clinic.
“We don’t know about potential side effects of this molecule,” Fiorin said. “It’s too early to know if it’ll work in patients.”
But the discovery can potentially benefit many patients down the line. According to the Centers for Disease Control and Prevention, an estimated 5-20 percent of the population gets the flu each year, and more than 200,000 people are hospitalized from flu-related complications.
If everything goes according to plan, the compound could reach the clinic in five years, Fiorin said.
“We know that the virus is evolving to resist Tamiflu so we can’t really wait too long,” he said.
In the meantime, Klein and his team are already thinking ahead. They plan on using computer simulations to predict new M2 mutations.
“It’s easy for us,” Fiorin said. “We don’t need to make a mutated virus in the lab, we can test it on the computer.”
Liora Engle-Smith can be reached at firstname.lastname@example.org