Fortunately, scientists at the National High Magnetic Field Laboratory and Institute of Molecular Biophysics at Florida State University and researchers at Brigham Young University in Utah are close to understanding why these drugs have become less effective — and how new drugs might take their place. Their findings appear this week in the journal Science.
"Resistance to drugs is a fundamental problem that develops from their misuse, overuse and underuse," said Timothy A. Cross, the Earl Frieden Professor of Chemistry and Biochemistry at Florida State and director of the Magnet Lab's Nuclear Magnetic Resonance Program, as well as one of the Science article's senior authors. Compounding the problem is that "the development of new drugs to take their place is a decade-long process with infrequent success."
The two drugs no longer recommended by the U.S. Centers for Disease Control — amantadine (brand names Symadine and Symmetrel) and rimantadine (Flumadine) — have been used to fight the flu since 1969. For decades, they worked by preventing an essential protein function during viral infection of healthy cells. The protein, called the M2 channel, plays a key role in the virus' ability to reproduce. But the M2 channel mutated just enough to allow the virus to resist both drugs.
"Our work provides a blueprint on how protons are moved through a passageway inside the M2 channel," said Huan-Xiang Zhou, an FSU physics professor and the other senior co-author of the Science article. Interfering with that passageway is "an obvious route for drug development."
To study the M2 channel, researchers enlisted the help of one of the magnet lab's crown jewels: the 900-megahertz, nuclear magnetic resonance magnet. The 40-ton magnet was used to map the protein's structure by giving it the equivalent of an MRI scan. The detailed images allowed the research groups of Cross and Zhou to chart the tiniest, previously unknown aspects of the protein's atomic structure.
"Now that we have a much more refined view of M2 — going all the way down to the atomic level, the level that includes protons going through the channel — we can draw conclusions about how to block it," said David Busath, a biophysicist at Brigham Young University and a co-author of the Science paper.
As to why the longtime flu drugs have become ineffective, the massive misuse of amantadine in poultry may have played a role, Cross said.
In the West, amantadine can only be given to humans. But starting in 2005, the Chinese began feeding it to chickens and other poultry to prevent them from getting avian flu. In all, China administered 2.6 billion doses of amantadine to its domestic birds.
"It's terrible to utilize these miracle drugs that can save thousands, if not millions, of lives and dramatically reduce hospitalizations in that fashion," Cross said.
The flu project headed up by Cross, Zhou and Busath is paid for by a 10-year, multimillion-dollar grant from the National Institutes of Health. Additional contributors to the Science article are lead author Mukesh Sharma, Myunggi Yi, Hao Dong and Huajun Qin, all of FSU, and Emily Peterson of BYU.
The National High Magnetic Field Laboratory develops and operates state-of-the-art, high-magnetic-field facilities that faculty and visiting scientists and engineers use for research. The laboratory is sponsored by the National Science Foundation and the state of Florida.
Immune Defense Without Collateral Damage
23.01.2017 | Universität Basel
The interactome of infected neural cells reveals new therapeutic targets for Zika
23.01.2017 | D'Or Institute for Research and Education
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
23.01.2017 | Health and Medicine
23.01.2017 | Physics and Astronomy
23.01.2017 | Process Engineering