Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Key target for Foot and Mouth drug revealed

21.03.2005


A complete picture of Foot-and-Mouth Disease’s key replication enzyme could lead to the development of new drugs to control the disease without recourse to vaccination or slaughter, scientists report today.



By solving the structure of the Foot-and-Mouth Disease Virus (FMDV) enzyme named ’3C protease’ scientists have taken an essential step towards developing protease inhibitors, a class of anti-viral drug that has proved hugely successful in controlling HIV.

The structure paves the way for their development by revealing the atomic details of the key viral enzyme that would serve as a target for drugs.


3C protease’s function is to help the virus replicate itself. A drug that binds and inhibits FMDV 3C protease would stop its spread by blocking its replication and thus its ability to infect a herd.

"In an outbreak we would ’dose up’ the animals and in theory they would be protected immediately," said Dr Stephen Curry of Imperial College London and senior author of the research paper, published in Journal of Biological Chemistry this week. "In contrast, vaccines take several days to have effect and that allows further spread of the disease."

"Our work is a very first step in developing an effective drug to do this. We can see what the enzyme looks like and it gives us an idea of what sort of shapes and types of molecule could bind specifically to the enzyme and block it."

The Imperial researchers are now designing a molecule to act as an inhibitor.

Together with Professor Robin Leatherbarrow of the Department of Chemistry, Dr Curry’s team from the Division of Cell and Molecular Biology has probed the specificity of the 3C enzyme in the hope of developing peptide-like inhibitors, similar to those successful in tackling HIV. Professor Leatherbarrow is mapping out the key amino acid sequences that the protease snips in-between, a process called ’peptide cleavage analysis’.

"We’ve determined the key features of peptides that are recognised by the FMDV 3C protease. Now we can start working on making the inhibitors," said Dr Curry.

During the devastating outbreak of Foot-and-Mouth in the UK in 2001, there was much debate as to whether vaccines should be used to control the disease. They were not deployed and the government relied on mass slaughter of five million animals to bring the epidemic under control.

Protease inhibitors were developed against HIV in the 1980s and 1990s, the first going on sale in 1996. However, interactions between the drugs and the HIV virus have given rise to drug-resistant strains, reducing the treatment’s effectiveness.

Although the same strategy is being adopted, Dr Curry does not foresee the same happening with an FMDV protease inhibitor due to the intrinsic differences between the diseases:

"HIV is a very long term infection, taking 10-15 years to overwhelm the body. That gives the virus plenty of time to develop resistance to anti-viral drugs. FMDV is highly contagious, much easier to get than HIV, and has a rapid onset, which is why outbreaks tend to spread so rapidly," said Dr Curry. "If you wanted to control an FMDV outbreak you could in theory swamp the livestock population with anti-viral drugs for a few weeks and hopefully eradicate the outbreak very quickly."

The 23,000 Dalton (weight) enzyme, is made of 213 amino acids, and is folded into a classic protease form, similar to those seen in poliovirus, hepatitis A virus and human rhinovirus, the major cause of the common cold.

The structure took over four years to solve, the start of research pre-dating the 2001 Foot-and-Mouth outbreak. The greatest problems came in making crystals of the 3C protease so that its structure could be solved by X-ray crystallography -- a particularly taxing task to solve for then beginning PhD student and first author of this paper, Dr James Birtley.

The work was supported by the Biological and Biotechnological Sciences Research Council, the Fleming Fund (Imperial College London), and the Medical Research Council.

Tom Miller | alfa
Further information:
http://www.imperial.ac.uk

More articles from Life Sciences:

nachricht A new molecular player involved in T cell activation
07.12.2018 | Tokyo Institute of Technology

nachricht News About a Plant Hormone
07.12.2018 | Julius-Maximilians-Universität Würzburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

Im Focus: Three components on one chip

Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.

Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...

Im Focus: Substitute for rare earth metal oxides

New Project SNAPSTER: Novel luminescent materials by encapsulating phosphorescent metal clusters with organic liquid crystals

Nowadays energy conversion in lighting and optoelectronic devices requires the use of rare earth oxides.

Im Focus: A bit of a stretch... material that thickens as it's pulled

Scientists have discovered the first synthetic material that becomes thicker - at the molecular level - as it is stretched.

Researchers led by Dr Devesh Mistry from the University of Leeds discovered a new non-porous material that has unique and inherent "auxetic" stretching...

Im Focus: The force of the vacuum

Scientists from the Theory Department of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science (CFEL) in Hamburg have shown through theoretical calculations and computer simulations that the force between electrons and lattice distortions in an atomically thin two-dimensional superconductor can be controlled with virtual photons. This could aid the development of new superconductors for energy-saving devices and many other technical applications.

The vacuum is not empty. It may sound like magic to laypeople but it has occupied physicists since the birth of quantum mechanics.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

Expert Panel on the Future of HPC in Engineering

03.12.2018 | Event News

Inaugural "Virtual World Tour" scheduled for december

28.11.2018 | Event News

 
Latest News

A new molecular player involved in T cell activation

07.12.2018 | Life Sciences

High-temperature electronics? That's hot

07.12.2018 | Materials Sciences

Supercomputers without waste heat

07.12.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>