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.
Discovery of a Key Regulatory Gene in Cardiac Valve Formation
24.05.2017 | Universität Basel
Carcinogenic soot particles from GDI engines
24.05.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
24.05.2017 | Physics and Astronomy
24.05.2017 | Physics and Astronomy
24.05.2017 | Event News