The results are to be published in the Journal of Medicinal Chemistry and are now online.
Previous studies have shown that small molecules can interfere with the Ebola infection process, says Duncan Wardrop, associate professor of chemistry at UIC and corresponding author of the new study. But almost all of these compounds "appear to exert their effects by altering the cells' response to the virus once it's entered the cell -- by which time it's too late," he said.
The new findings demonstrate that it is possible for a small molecule to bind to the virus before it has a chance to enter the cell and thereby prevent infection, he said.
Wardrop collaborated with UIC virologist Lijun Rong, who created a screening system that uses a chimeric HIV-Ebola virus bearing the protein coat of the Ebola virus. The chimera looks like Ebola but isn't life-threatening for scientists to work with.
After screening more than 230 candidate compounds, Wardrop and Rong found two molecules that inhibited cell entry, but only one that demonstrated specificity for the Ebola virus -- plus a bonus.
"We found that our lead compound also inhibits Marburg," Wardrop said, referring to a related virus that, along with Ebola, is one of the deadliest pathogens known. "That was a nice surprise. There's growing evidence the two viruses have the same cell-entry mechanism, and our observations appear to point to this conclusion."
In an effort to find even more potent anti-Ebola agents, Wardrop and graduate student Maria Yermolina synthesized a series of derivatives of the lead molecule -- a member of a family of compounds called isoxazoles -- and found several that displayed increased activity against Ebola infection. Exactly how and where these small molecules bind to the virus's protein coat is now being determined through nuclear magnetic resonance spectroscopy, done by Michael Caffrey, associate professor of biochemistry and molecular genetics.
While it's too early to predict whether the findings will lead to a new treatment for Ebola or Marburg infections, Wardrop said the positive results so far raise hope. The next step would be to see if small-molecule treatments prove effective in animal models.
The UIC scientists also hope their findings will provide further insight into mechanisms the Ebola and Marburg viruses use to enter human cells.
"This knowledge may spur development of new anti-viral agents," Wardrop said.
"From a wider perspective, we're searching for compounds to use as probes to study biological processes. Small molecules which bind to specific proteins and alter their function are invaluable to understanding what these proteins do in living cells," he said.
Paul Francuch | 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