Biomedical researchers at the University of Texas Medical Branch at Galveston (UTMB) have taken an important early step toward developing effective drug therapies against Venezuelan Equine Encephalitis (VEE) virus, a potential bioterrorist weapon. Their achievement: determining the precise structure of a protein that the virus requires for replication.
Outbreaks of the mosquito-borne VEE virus periodically ravage Central and South America, infecting tens of thousands of people and killing hundreds of thousands of horses, donkeys and mules. Experts also fear VEE's potential as a weapon of bioterrorism because the virus was developed into a biological weapon during the Cold War by both the United States and the Soviet Union. Analysts fret that terrorists could do likewise.
The protein the scientists focused on is known as the nsP2 protease. It acts like a pair of molecular scissors, chopping another complex of VEE proteins into specific smaller protein molecules that work together to transform living cells into VEE virus factories. "This protein is crucial to VEE virus replication, and we want to create drugs that will turn off such proteins," said Stanley W. Watowich, senior author of a paper on the research to be published in the September 12 issue of the journal Structure. The UTMB associate professor of biochemistry and molecular biology added, "Now that we know what this protease looks like, we can begin a systematic computer-based search for compounds that will inhibit its activity, stop the virus from multiplying in infected individuals, and prevent VEE outbreaks from spreading."
VEE protease inhibitors would function much like the protease inhibitors taken by people infected with HIV, Watowich said, but since human and equine immune systems could quickly overwhelm VEE viruses that were unable to replicate, infections would be eliminated instead of merely controlled, and permanent use of the medication would be unnecessary. (Those infected would also acquire immunity to VEE, just as if they had been vaccinated with a weakened form of the virus.)
Potential therapeutic compounds could be available for pre-clinical studies within two years, according to Watowich, thanks to collaborations with powerful computer centers at the University of Texas at Austin and IBM that will be able to take the UTMB protease structure and sift through "libraries" of millions of molecules, looking for those with the right structural and chemical characteristics to keep the "scissors" from closing.
To produce a detailed enough structure to begin this drug search, lead author and Watowich lab postdoctoral fellow Andrew Russo used X-ray crystallography, in which X-rays are used to scan crystallized protein samples, working both with equipment at UTMB and the high power synchrotron radiation source at Louisiana State University's Center for Advanced Microstructures and Devices in Baton Rouge. "It took about a year of hard work by Andrew, but it was worth it," Watowich said. "In the future when we're dealing with one of these periodic VEE outbreaks or a bioterrorist attack, it will be a very good thing if we have an effective medicine in the cabinet ready to use."
Jim Kelly | EurekAlert!
Cancer diagnosis: no more needles?
25.05.2018 | Christian-Albrechts-Universität zu Kiel
Less is more? Gene switch for healthy aging found
25.05.2018 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
The more electronics steer, accelerate and brake cars, the more important it is to protect them against cyber-attacks. That is why 15 partners from industry and academia will work together over the next three years on new approaches to IT security in self-driving cars. The joint project goes by the name Security For Connected, Autonomous Cars (SecForCARs) and has funding of €7.2 million from the German Federal Ministry of Education and Research. Infineon is leading the project.
Vehicles already offer diverse communication interfaces and more and more automated functions, such as distance and lane-keeping assist systems. At the same...
A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.
The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
25.05.2018 | Event News
02.05.2018 | Event News
13.04.2018 | Event News
25.05.2018 | Event News
25.05.2018 | Machine Engineering
25.05.2018 | Life Sciences