Findings to help in design of drugs against virus causing childhood illnesses
New research findings may help scientists design drugs to treat a virus infection that causes potentially fatal brain swelling and paralysis in children.
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 fatal encephalitis in infants and young children, primarily in the Asia-Pacific region.
Currently, no cure exists for the infection.
New findings show the precise structure of the virus bound to a molecule that inhibits infection. The findings are detailed in a paper appearing this week in Proceedings of the National Academy of Sciences.
"These results provide a structural basis for development of drugs to fight enterovirus 71 infection," said Michael G. Rossmann, Purdue University's Hanley Distinguished Professor of Biological Sciences.
Rossmann is co-author of a paper with Purdue postdoctoral research associate Pavel Plevka; research scientist Rushika Perera; postdoctoral research associate Moh Lan Yap; Jane Cardosa, a researcher at Sentinext Therapeutics in Malaysia; and Richard J. Kuhn, a professor and head of Purdue's Department of Biological Sciences.
The researchers had previously used a technique called X-ray crystallography to determine the virus's precise structure. A small molecule called a "pocket factor" is located within a pocket of the virus's protective shell, called the capsid. When the virus binds to a human cell, the pocket factor is squeezed out of its pocket resulting in the destabilization of the virus particle, which then disintegrates and releases its genetic material to infect the cell and replicate.
Researchers led by Rossmann have developed antiviral drugs for other enteroviruses such as rhinoviruses 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, inhibiting infection. In the new work, the researchers obtained a near-atomic-scale resolution three-dimensional structure of enterovirus 71 binding with an inhibitor called WIN 51711.
"We show that the compound stabilizes the virus and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release," Rossmann said. "Our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs."
At a resolution of 3.2 angstrom, the images show nearly atomic-scale structural features.
Hand, foot and mouth disease, an infection most common among young children, sometimes arises in a daycare setting. Of the 427,278 cases of the disease recorded in mainland China between January and May 2010, 5,454 cases were classified as severe, with 260 deaths, according to the World Health Organization.
More information: Structure of Human Enterovirus 71 in Complex with a Capsid-Binding Inhibitor, Proceedings of the National Academy of Sciences, 2013.
Human enterovirus 71 is a picornavirus causing hand, foot and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-Å-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs.
Journal reference: Proceedings of the National Academy of Sciences
Provided by Purdue University
- Studies reveal structure of EV71, a virus causing childhood illnesses Mar 02, 2012 | not rated yet | 0
- Scientists learn structure of enzyme in unusual virus Sep 17, 2007 | not rated yet | 0
- Biologists spy close-up view of poliovirus linked to host cell receptor Dec 08, 2008 | not rated yet | 0
- Researchers unravel structure of 'Sputnik' virus, could have implications for treatment Nov 07, 2012 | not rated yet | 0
- New findings detail how virus prepares to infect cells Dec 01, 2010 | not rated yet | 0
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
9 hours ago From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
In 2008 researchers from the University of Southern Denmark showed that the drug thioridazine, which has previously been used to treat schizophrenia, is also a powerful weapon against antibiotic-resistant bacteria such as ...
Medical research 20 hours ago | 3.7 / 5 (3) | 0 |
Scientists investigating the interaction of a group of proteins in the brain responsible for protecting nerve cells from damage have identified a new target that could increase cell survival.
Medical research May 17, 2013 | 5 / 5 (1) | 0
New findings by researchers carrying out experiments at the U.S. Department of Energy Office of Science's Advanced Photon Source (APS) help explain why some drugs that interact with two kinds of human serotonin ...
Medical research May 17, 2013 | not rated yet | 0 |
Peptide molecules derived from the body's natural immune system can help boost the body's defence against life-threatening blood poisoning, joint University research has uncovered.
Medical research May 17, 2013 | 4 / 5 (1) | 0 |
A new Montréal study conducted by Dr. May Faraj, associate research professor at the Université de Montréal and invited scientist at the IRCM, along with her research team and medical collaborators, shows ...
Medical research May 17, 2013 | not rated yet | 0 |
7 seconds ago | not rated yet | 0
20 minutes ago | not rated yet | 0
2 hours ago | not rated yet | 0 |
2 hours ago | 5 / 5 (1) | 0
10 hours ago | 5 / 5 (1) | 0
11 hours ago | 5 / 5 (1) | 0 |