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!
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25.09.2018 | Deutsches Primatenzentrum GmbH - Leibniz-Institut für Primatenforschung
The Fraunhofer FEP has been involved in developing processes and equipment for cleaning, sterilization, and surface modification for decades. The CleanHand Network for development of systems and technologies to clean surfaces, materials, and objects was established in May 2018 to bundle the expertise of many partnering organizations. As a partner in the CleanHand Network, Fraunhofer FEP will present the Network and current research topics of the Institute in the field of hygiene and cleaning at the parts2clean trade fair, October 23-25, 2018 in Stuttgart, at the booth of the Fraunhofer Cleaning Technology Alliance (Hall 5, Booth C31).
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This is a joint press release of University Muenster and Heidelberg as well as the GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt.
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A study in the journal Bulletin of Marine Science describes a new, blood-red species of octocoral found in Panama. The species in the genus Thesea was discovered in the threatened low-light reef environment on Hannibal Bank, 60 kilometers off mainland Pacific Panama, by researchers at the Smithsonian Tropical Research Institute in Panama (STRI) and the Centro de Investigación en Ciencias del Mar y Limnología (CIMAR) at the University of Costa Rica.
Scientists established the new species, Thesea dalioi, by comparing its physical traits, such as branch thickness and the bright red colony color, with the...
Scientists have succeeded in observing the first long-distance transfer of information in a magnetic group of materials known as antiferromagnets.
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25.09.2018 | Life Sciences
25.09.2018 | Life Sciences
25.09.2018 | Life Sciences