Issue Date: July 4, 2011
Virtual Drug Screen Targets Flexible RNAs
A technique to find compounds that interact with specific RNA conformations has led to an agent with in vivo anti-HIV activity (Nat. Chem. Biol., DOI: 10.1038/nchembio.596). RNAs are much more flexible structurally than proteins and are therefore challenging “moving targets” for drug discovery. Several research groups have analyzed the range of conformations associated with specific RNAs, but progress has been limited in finding bioactive molecules that interact with them. Hashim M. Al-Hashimi of the University of Michigan and coworkers have now combined NMR and computational molecular dynamics to analyze the different forms adopted by transactivation response element (TAR), a key component of HIV’s RNA genome. They used virtual screening to predict compounds most likely to bind these forms and found six candidates that bind with high affinity and selectivity. One of these molecules, the antibiotic netilmicin, inhibits HIV replication in human T cells. The screening technique, which has been licensed exclusively to Nymirum, a biotech company based in Ann Arbor, Mich., that Al-Hashimi cofounded, could prove useful for finding other compounds that interact with biologically important RNAs.
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