某小分子群可能预防埃博拉病毒感染

Ebola, a virus that causes deadly hemorrhagic fever（出血热） in humans, has no known cure or vaccine¹. But a new study by University of Illinois at Chicago scientists has uncovered a family of small molecules³ which appear to bind⁴ to the virus's outer protein coat and may inhibit⁵ its entry into human cells. The results are to be published in the Journal of Medicinal Chemistry and are now online.

Previous studies have shown that small molecules can interfere⁶ with the Ebola infection process, says Duncan Wardrop, associate professor of chemistry at UIC and corresponding author of the new study. But almost all of these compounds "appear to exert（运用，发挥） their effects by altering the cells' response to the virus once it's entered the cell -- by which time it's too late," he said.

The new findings demonstrate that it is possible for a small molecule² to bind to the virus before it has a chance to enter the cell and thereby⁷ prevent infection, he said.

Wardrop collaborated⁸ with UIC virologist Lijun Rong, who created a screening system that uses a chimeric⁹（妄想的） HIV-Ebola virus bearing the protein coat of the Ebola virus. The chimera¹⁰ 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 inhibited¹¹ cell entry, but only one that demonstrated specificity for the Ebola virus -- plus a bonus.

"We found that our lead compound also inhibits¹² Marburg," Wardrop said, referring to a related virus that, along with Ebola, is one of the deadliest pathogens（病原体） known. "That was a nice surprise. There's growing evidence the two viruses have the same cell-entry mechanism¹³, and our observations appear to point to this conclusion."

In an effort to find even more potent¹⁴ anti-Ebola agents, Wardrop and graduate student Maria Yermolina synthesized a series of derivatives¹⁵ of the lead molecule -- a member of a family of compounds called isoxazoles -- and found several that displayed increased activity against Ebola infection. Exactly how and where these small molecules bind to the virus's protein coat is now being determined¹⁶ through nuclear magnetic resonance¹⁷ spectroscopy（光谱学） , done by Michael Caffrey, associate professor of biochemistry and molecular¹⁸ genetics.

While it's too early to predict whether the findings will lead to a new treatment for Ebola or Marburg infections, Wardrop said the positive results so far raise hope. The next step would be to see if small-molecule treatments prove effective in animal models.

The UIC scientists also hope their findings will provide further insight into mechanisms¹⁹ the Ebola and Marburg viruses use to enter human cells.

"This knowledge may spur development of new anti-viral agents," Wardrop said.

"From a wider perspective, we're searching for compounds to use as probes to study biological processes. Small molecules which bind to specific proteins and alter their function are invaluable²⁰ to understanding what these proteins do in living cells," he said.