TB-Drugome May Pave Way for Anti-TB Drug Discovery

A study by researchers at the University of Leeds, United Kingdom, and the University of California, San Diego, School of Medicine, United States, showed that one third of the existing drugs examined have potential to be repurposed to treat TB. The scientists used a novel computational strategy to investigate whether any existing drugs could bind to any of the approximately 50 percent of proteins in the M. tuberculosis (Mtb) proteome with decipherable three-dimensional structures. The results linked hundreds of federally approved drugs to more than 1,000 proteins in Mtb. The investigators then constructed a complex network of drug-target interactions, a TB-drugome, available to all scientists. Although the new process of drug discovery is promising, one of the research scientists, Lei Xie of the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego, warned that only experimentation can validate the most promising drug-target combinations, and there will be many failures along the way. Also, Sarah Kinnings of the University of Leeds noted that drugs confirmed to bind to Mtb proteins might need to be modified, to increase their ability to penetrate the bacterial cell membrane, reduce the required dosage, and improve other pharmacological properties. This article was published in the journal PLoS Computational Biology 6(11): e1000976. doi:10.1371/journal.pcbi.1000976