Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A ‘finger’ pointing the way to new hepatitis C medication

09.11.2012
Braunschweig scientists develop compounds with potential against Hepatitis C virus

Some 160 million men and women are infected with Hepatitis C virus (HCV), the most common cause of cirrhosis and cancer of the liver. The present standard therapy is thraught with serious side-effects leading to a cure in only half of the patients. New therapies utilise small molecules that inhibit specific steps in the viral reproduction. However, the pathogen rapidly develops resistance, becoming insensitive to these agents.


HCV-infected cells: green, fat-droplets, in which the virus is being assembled; red, parts of the virus; blue, the liver cell nucleus
TWINCORE / T. Pietschmann

Researchers at the Helmholtz Centre for Infection Research (HZI) in Braunschweig, in collaboration with colleagues from the TWINCORE in Hannover have discovered new drug leads that are also efficient against resistant virus. They present their work in the Journal of Biological Chemistry.

Interferons are used as classic medication against HCV as well as a few other viruses. Some interferons are produced naturally in the body in response to viral infection, others as immune modulators during inflammation. However, therapy with interferon is expensive, takes many months and has undesirable and unpleasant side effects. Hope was generated during the last few years through the development of a new generation of small drugs directed directly to the virus, in particular to those inhibiting the viral protease. These compounds inhibit viral replication by preventing the formation of the functional and structural components that must be cut out a precursor which the HCV virus instructs the host cell to produce in a single ‘block’. This cutting, or processing, is initiated by the viral protease which mutates rapidly, generating resistant variants for which the protease-inhibitors have lost their effectivity.

Scientists from the group of Prof. John Collins at the HZI have succeeded in identifying novel small molecules that are active against HCV. “Our molecules use several sites of action in inhibiting the viral protease. Amongst these one which had not previously been addressed by existing protease inhibitors,” explains Dr. Jonas Kügler, one of the participating scientists from the HZI. “Thus our molecules are effective against resistant virus with the expectation that the development of resistance will be more difficult,” adds his colleague Dr. Stefan Schmelz from the group of Prof. Dirk Heinz. Kügler and Schmelz are the first authors on the publication. This work is a colaboration between the groups of Collins and Heinz and scientists from the TWINCORE, Hannover, in the institute of Prof. Thomas Pietschmann.

The development of the novel inhibitors used an approach which combined two different tactics: In one special iterative enrichment process using ‘empirical selection’, the scientists searched for small proteins that bound specifically to the desired target: the HCV protease. During the second step, suitable candidates were then slightly modified on the basis of ‘rational design’ and thus further optimized for the desired property. This resulted in molecules that have a strong inhibitory effect on the protease when added at a very low concentration. All of the molecules share a novel structural feature which the researchers call a ‘tyrosine-finger’. This binds a region in the viral protease that was not bound by other inhibitors previously investigated.

“We do not expect that these molecules can be directly used for clinical antiviral therapy“ says John Collins. “Our results are, however, of great significance for the development of novel therapeutics effective even on virus resistant to other small inhibitors.” In the continuing race between the virus and the scientists, the researchers have achieved a new head-lead, or should one say a finger that points in the right direction.

Original publication:
Jonas Kügler, Stefan Schmelz, Juliane Gentzsch, Sibylle Haid, Erik Pollmann, Joop van den Heuvel, Raimo Franke, Thomas Pietschmann, Dirk W. Heinz and John Collins
High affinity peptide inhibitors of the hepatitis C virus NS3-4A protease refractory to common resistant mutants
Journal of Biological Chemistry, 2012
DOI: 10.1074/jbc.M112.393843

Dr. Jan Grabowski | Helmholtz Zentrum
Further information:
http://dx.doi.org/10.1074/jbc.M112.393843
http://www.helmholtz-hzi.de/en/news_events/news/view/article/complete/a_finger_pointing_the_way_to_new_hepatitis_c_medication/

More articles from Life Sciences:

nachricht Complementing conventional antibiotics
24.05.2018 | Goethe-Universität Frankfurt am Main

nachricht Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

When corals eat plastics

24.05.2018 | Ecology, The Environment and Conservation

Surgery involving ultrasound energy found to treat high blood pressure

24.05.2018 | Medical Engineering

First chip-scale broadband optical system that can sense molecules in the mid-IR

24.05.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>