Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme inhibitors block replication of SARS virus

29.03.2006
Finding could help speed SARS drug discovery

The study was conducted by researchers from Scripps Research; the Genomics Research Center, Academia Sinica, Taiwan; and the National Taiwan University. It is being published today in the journal Chemistry and Biology (Vol. 13, No. 3).

Chi-Huey Wong is currently the Ernest W. Hahn Chair in Chemistry at the Skaggs Institute of Chemical Biology and directs the Scripps Research lab heading the study. He said the new finding is an important step in developing a possible drug treatment against SARS.

"We have been working on the problem of SARS since the epidemic started in 2003," Wong said. "This new class of inhibitors represents the most potent SARS virus protease inhibitors known today."

The path to today’s research finding has taken several years. In 2002, Severe Acute Respiratory Syndrome (SARS) emerged in rural China and eventually spread to 32 countries, according to the World Health Organization. SARS is caused by a ring-shaped virus, known as a coronavirus. The SARS coronavirus is suspected of originating in animal populations before migrating to humans. Hardest-hit were six Asian nations. By the time the epidemic had been controlled in 2003, the disease infected more than 8,000 people, causing 800 deaths. There is no current effective treatment or vaccine.

Researchers have known since 2003 that a site on the virus is responsible for mediating proteases that allow the virus to replicate. Since then researchers have been testing protease inhibitors to lock up this site, known as SARS 3CLpro, and effectively stop the virus from infecting additional cells in the body.

In 2004, Wong’s lab discovered that Lopinavir, a protease inhibitor of HIV also known as TL3, also served as weak inhibitor of the SARS 3CLpro site (PNAS, 101, 10012-10017). Since then, members of Wong’s group further studied Lopinavir and are preparing it for clinical trials against SARS.

Researchers in Wong’s lab at Scripps Research and in Taiwan have been looking at other Liponavir-related compounds for similar blocking effects. During these experiments, they found that a group of catalyzing agents used to help promote chemical reactions in the laboratory were actually more powerful in blocking the SARS protease than either the Lopinavir or any of the target compounds.

These organic compounds are called benzotriazole esters. The esters entered the SARS protease site, formed an intermediary compound, then inactivated the SARS enzyme. The findings were confirmed using mass spectrometry analysis of the enzyme intermediary.

"These benzotriazole esters are relatively stable and act as suicide inhibitors," Wong said. "They block the enzyme, are transformed through a co-valent bond, and are unable to get out."

Wong said the findings published today provide better insight into the mode of action of the enzyme, which may lead to development of a drug against SARS. The findings were made by using rapid drug discovery techniques developed in the Wong lab to screen large numbers of weak enzyme inhibitors, and then attaching additional compounds to look for stronger reactions.

Research Associate Chung-Yi Wu, a member of the Wong lab, is the paper’s lead author. He said the finding was unexpected.

"We wanted to improve Liponavir activity," Wu said. "But we found this very surprising and serendipitous result."

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

NASA looks to solar eclipse to help understand Earth's energy system

21.07.2017 | Earth Sciences

Stanford researchers develop a new type of soft, growing robot

21.07.2017 | Power and Electrical Engineering

Vortex photons from electrons in circular motion

21.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>