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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>