Wednesday, January 26, 2011

Small Molecules (Isoxazole derivatives) May Prevent Ebola Infection

A new study by University of Illinois at Chicago scientists has uncovered a family of small molecules (isoxazole derivatives), which appear to bind to the virus's outer protein coat and may inhibit its entry into human cells.
The new findings demonstrate that it is possible for a small molecule to bind to the virus before it has a chance to enter the cell and thereby prevent infection. Wardrop collaborated with UIC virologist Lijun Rong, who created a screening system that uses a chimeric HIV-Ebola virus bearing the protein coat of the Ebola virus. The chimera looks like Ebola but isn't life-threatening for scientists to work with.
After screening more than 230 candidate compounds, Wardrop and Rong found two molecules that inhibited cell entry, but only one that demonstrated specificity for the Ebola virus plus a bonus.

We found that our lead compound also inhibits Marburg," Wardrop said, referring to a related virus that, along with Ebola, is one of the deadliest pathogens known. "That was a nice surprise. There's growing evidence the two viruses have the same cell-entry mechanism, and our observations appear to point to this conclusion."
In an effort to find even more potent anti-Ebola agents, Wardrop and Maria Yermolina synthesized a series of derivatives of the lead molecule called isoxazoles. Researchers found that the compounds, displayed increased activity against Ebola infection. Though the mechanism of action of these class of compounds is still to be established, in my opinion its an achievement. More interestingly, the mode of study is being studied by nuclear magnetic resonance spectroscopy, done by Michael Caffrey, associate professor of biochemistry and molecular genetics. While it's too early to predict whether the findings will lead to a new treatment for Ebola or Marburg infections, the positive results so far raise the hope....

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