Striking new research from Rice University and the University of Texas at Austin (UT) has revealed a potential new target that drug makers can use to attack several strains of influenza, including those that cause bird flu as well as the common variety that infects millions each flu season.
"There is a small binding pocket for the tail loop of the protein that appears to be a promising target for a new class of antiviral drugs," said lead researcher Jane Tao, assistant professor in biochemistry and cell biology. "We know from previous genetic studies that this tail loop is almost identical across strains of influenza A, so drugs that target the tail have a high potential of being effective against multiple strains, including the H5N1 strains. Such new antivirals are especially needed at the moment as some H5N1 viruses are resistant to the flu drug Tamiflu."
Tao's findings are based on a painstaking series for experiments that revealed the atomic structure of NP. The protein's structure was discerned via X-ray crystallography, a method that allows scientists to discern the three-dimensional placement of atoms in a crystal based upon the diffraction patterns of X-rays that pass through it.
Tao said it was a challenge to growing NP protein crystals. The method used was the hanging drop vapor diffusion method, which involves suspending a liquid droplet of concentrated protein solution on the underside of a glass slide that is sealed inside a jar. As the liquid in the droplets evaporates, the proteins become supersaturated, and in some cases they form tiny crystals of a few hundred microns in size. Tao estimates that postdoctoral research associate Qiaozhen Ye prepared about 1,000 jars, with multiple droplets per jar, to get the 100 or so crystals that were needed for the experiments.
NP is one of only 11 proteins that are encoded by the influenza A genome. One of its main functions is structural. Once the virus has hijacked a host cell, and converted it into a virus-replicating factory, the NPs come together in small rings as building blocks. Many NP rings stack one atop the other in a slightly off-registered fashion, forming long helical-shaped columns. The virus's RNA genome is twisted around this column and shipped out to infect other cells.
"NP has about 500 amino acids and the tail loop contains about 30 of those," Tao said. "We found that a mutation in only one residue out of 30 was enough to prevent the NPs from coming together to form the building blocks for the columns, and without these columns the virus cannot make copies and infect other cells."
Tao said the research also provides clues about NP's role in signaling a cell to begin making copies of the viral genome, and Tao's group is continuing its work with co-author Robert Krug at the University of Texas at Austin to explore the protein's regulatory functions.
The research was funded by.the Welch Foundation, National Institutes of Health, and the Nanoscale Science and Engineering Initiative of the National Science Foundation.
Jade Boyd | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy