Researchers have discovered critical new details about the structure of a virus that causes potentially fatal brain swelling1(肿胀) and paralysis2 in children, pointing toward designs for antiviral drugs to treat the disease. The virus, called enterovirus 71, causes hand, foot and mouth disease, and is common throughout the world. Although that disease usually is not fatal, the virus has been reported to cause encephalitis, a potentially fatal illness found primarily in the Asia-Pacific region.
Now, two research teams are reporting new findings about the structure of the virus. One of the teams, from Purdue University, has proposed a way to design antiviral drugs to treat the infection. Findings from that team are detailed3 in a paper appearing March ) in the online Express issue of the journal Science. Another team, led by researchers at Oxford4 University, will report its findings in a paper scheduled to appear March 4 in the journal Nature Structural5 & Molecular6 Biology.
"Taken together, the findings in both papers are useful when you are trying to stop the virus from infecting host cells," said Michael G. Rossmann, Purdue's Hanley Distinguished7 Professor of Biological Sciences. "The common theme is that they both report for the first time on the structure of this virus, and this tells us how to design compounds to fight the infection."
Rossmann is co-author of a paper written by Purdue postdoctoral research associate Pavel Plevka; Purdue research scientist Rushika Perera; Richard J. Kuhn, a professor and head of Purdue's Department of Biological Sciences; and Jane Cardosa, a researcher at Sentinext Therapeutics in Malaysia.
Both teams used a technique called X-ray crystallography(晶体学) to determine the virus's precise structure, showing similarities to features on related enteroviruses(肠道病毒) , including poliovirus. However, a key feature is different in that a small molecule8 called a "pocket factor," located within a pocket of the protective shell of the virus, is partially9 exposed in EV71.
When the virus binds10 to a human cell, the pocket factor is squeezed out of its pocket resulting in the destabilization of the virus particle, which then disintegrates11 and releases its genetic12 material to infect the cell and replicate13.
Researchers led by Rossmann have developed antiviral drugs for other enteroviruses such as rhinoviruses(鼻病毒) that cause the common cold. The drugs work by replacing the pocket factor with a molecule that binds more tightly than the real pocket factor.