The study was published Nov. 4 in PLoS Computational Biology.
"Tuberculosis is currently one of the most widely spread infectious diseases, with an estimated one-third of the world's population infected and between one and two million people dying each year from the disease," said Philip Bourne, PhD, professor of pharmacology at UCSD's Skaggs School of Pharmacy and Pharmaceutical Sciences.
"The continuing emergence of M. tuberculosis strains resistant to all existing, affordable drug treatments requires the development of novel, effective and inexpensive drugs.
The newly developed TB-drugome may help that effort, Bourne said, by identifying new M. tuberculosis protein targets that can be perturbed by a variety of existing drugs prescribed for other purposes.
Sarah Kinnings at the University of Leeds and a team of scientists at UC San Diego, led by Bourne (who is also associate director of the RCSB Protein Data Bank) and research scientist Lei Xie, PhD, used a novel computational strategy to investigate whether any existing drugs were able to bind to any of the approximately 40 percent of proteins in the M. tuberculosis proteome with decipherable three-dimensional structures.
The researchers not only discovered that approximately one-third of the drugs examined may have the potential to be repurposed to treat tuberculosis, but also that many currently unexploited M. tuberculosis proteins could serve as novel anti-tubercular targets. This finding led the investigators to construct a complex network of drug-target interactions – a TB-drugome available to all scientists.
While this new computational, high-throughput process of drug discovery is promising, Xie cautioned that "only experimentation can validate the most promising drug-target combinations, and there will be many failures along the way."
Kinnings added that any drugs subsequently confirmed to bind to M. tuberculosis proteins may need to be modified to increase their ability to penetrate the bacterial cell membrane, reduce their required dosage, and improve other pharmacological properties. The screening of a large collection of analogs to known drugs will be the next step towards anti-tuberculosis drug discovery.
Other authors of the study are Richard Jackson of the Institute of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology at University of Leeds; Li Xie of the Skaggs School of Pharmacy and Pharmaceutical Sciences at UC San Diego and Kingston Fung of the UCSD's Bioinformatics Program.
Funding for this project came from the National Institutes of Health.
Scott LaFee | EurekAlert!
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
24.02.2017 | Life Sciences
24.02.2017 | Life Sciences
24.02.2017 | Trade Fair News