Scientists use powerful nuclear magnetic resonance magnets to study the influenza A virus and create new drugs to fight it.
Scientists at Florida State University (FSU) and Brigham Young University (BYU) have used one of the world’s most powerful nuclear magnetic resonance magnets to potentially unlock the mystery behind why two once-potent antiviral drugs -- amantadine and rimantadine -- are no longer effective against the influenza A virus.
According to a news release from the Florida State University Magnet Lab Media Center, scientists at the National High Magnetic Field Laboratory and Institute of Molecular Biophysics at Florida State University “are close to understanding why these drugs no longer work -- and how new drugs might.” Amantadine and rimantadine worked by disrupting the M2 channel protein, which “plays a key role” in the reproduction of the influenza A virus, and “preventing an essential protein function during viral infection of healthy cells.” However, over time, mutations to the M2 channel led to a drug-resistant form of the virus.
Now, the researchers from FSU and BYU have published their findings about the structure of the M2 channel protein in an article titled “Insight into the Mechanism of the Influenza A Proton Channel from a Structure in a Lipid Bilayer,” which appears appears in the October 22 issue of Science.
FSU physics professor Huan-Xiang Zhou, PhD, senior co-author of the article, said that this research “provides a blueprint on how protons are moved through a passageway inside the M2 channel,” and points to “an obvious route for drug development." The news release accompanying publication of the article reported that the researchers used the powerful magnet to “map the protein's structure by giving it the equivalent of an MRI scan,” allowing them to “chart the tiniest, previously unknown aspects of the protein's atomic structure.”
This unprecedented look at the atomic-level functioning of the influenza A virus and the M2 channel protein will allow researchers to investigate ways of blocking it, said BYU biophysicist and co-author of the Science paper David Busath, MD.
Click here to watch a video interview with David Busath, in which he says that “This work is laying a foundation to understand how that mutation does its damage and then of course how we can respond with a new bullet… Now we’ve got a fine enough resolution on the target we can start shooting at it, so to speak.” The news release that accompanies the video interview also notes that “Another appeal of the channel as a drug target is that there are only a limited number of ways it could mutate in the future and continue to function. So it’s possible that blockers could be identified in advance to defeat the virus no matter how it changes.”
Busath and colleagues have “already begun screening millions of compounds, looking for drugs that will bind to the channel and block its reproductive role;” FSU has been awarded two patents for drug screening.
The issue of Science in which this research was published also features two additional articles on the influenza A virus and the M2 channel protein: “The Flu’s Proton Escort,” by Fiorin, et al, and “Mechanisms of Proton Conduction and Gating in Influenza M2 Proton Channels from Solid-State NMR,” by Hu et al.