Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

From blank round to a potently active substance?

19.04.2013
A long-forgotten candidate for antiviral therapy is undergoing a renaissance: Since the 1970s, the small molecule CMA has been considered a potent agent against viral infections, yet it was never approved for clinical use.

Scientists at the Bonn University Hospital have now deciphered how the molecule can actually stimulate the immune system to combat viruses. The results are now being presented in the journal “EMBO” of the European Molecular Biology Organization.

Finding an active substance to stimulate the immune system and thus better combat dangerous viruses has been the dream of medical researchers for some time. Common viral diseases include influenza, hepatitis and AIDS. “A number of products have promised to activate the immune system but, in reality, there still is no such agent yet,” says Prof. Dr. Veit Hornung from the Institute for Clinical Chemistry and Clinical Pharmacology of the Bonn University Hospital.

The only substances that have been on the market to date prevent the proliferation of specific viruses, themselves. An active substance that could arm the immune system against a variety of viruses has not yet been discovered.

The compound CMA was only effective in mice and not in humans

At the end of the 1970s, scientists were nearing a breakthrough: 10-carboxymethyl-9-acridanone (CMA) appeared to be a suitable candidate for antiviral therapy. In the mouse model, CMA yielded unexpectedly potent activation of the immune system and a significant release of interferon resulting in an extremely strong antiviral effect. However, the result was unfortunately not reproducible in human cells. Why CMA stimulates the antiviral response in mice while showing no effect in humans has remained unexplained for quite sometime. That is until Prof. Hornung coincidentally saw an old publication regarding CMA and decided it was worthwhile to reexplore the mechanism of action of this molecule.

The same receptor - differing mechanism of action

Prof. Hornung believed that the lack of transferability between mice and humans might be associated with the specific target structures that CMA latches on to. The team working with Prof. Hornung was then able to identify the protein to which CMA attaches, its receptor, in mouse cells. However, the human counterpart of this receptor did not respond to CMA. When CMA binds to the receptor in mice, a signal cascade is set into motion that leads to the release of interferons which in turn boost the immune system. However, in order for this to work, CMA and its receptor must fit together like a lock and key. Together with the laboratory of Prof. Dr. Karl-Peter Hopfner from the Gene Center at the Ludwig Maximilian University in Munich, the team from the Bonn University Hospital investigated the receptor variants of mice and humans in cell cultures and as purified proteins.
Animal models cannot easily be transferred to humans

“A few small differences in the receptor make the active substance completely ineffective in humans,” reports lead author Taner Cavlar, postgraduate in Prof. Hornung’s team. In humans, this prevents CMA from being able to latch its crucial receptor and release interferon, even though immune stimulation occurs in mice. “This is an example of the fact that results from animal models cannot always be easily transferred to humans,” says Prof. Hornung. “Comparative investigations on human cells should take place at an early stage of active substance development.”

Findings inspire the search for an antiviral drug

Since the scientists were able to figure out the exact structure of the mouse and human receptors, they now have an approach to see if there are conditions under which CMA could also arm the human immune system to fight viruses. This is now the next step which the researchers want to address with their colleagues. However, it will likely take many years until an effective drug to combat viruses becomes available. “Nevertheless, when we are able to develop such a potent substance, only very small amounts would be enough to fight a variety of viral infections early on,” says Prof. Hornung.
Publication: Species-specific detection of the antiviral small-molecule compound CMA by STING, The EMBO Journal, DOI: 10.1038/emboj.2013.86

Contact information:

Prof. Dr. Veit Hornung
Institute for Clinical Chemistry and Clinical Pharmacology
of the Bonn University Hospital
Tel. +49-228-28751200
E-Mail: veit.hornung@uni-bonn.de

Johannes Seiler | idw
Further information:
http://www.uni-bonn.de

More articles from Health and Medicine:

nachricht A promising target for kidney fibrosis
21.04.2017 | Brigham and Women's Hospital

nachricht Stem cell transplants: activating signal paths may protect from graft-versus-host disease
20.04.2017 | Technische Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

Im Focus: Quantum-physical Model System

Computer-assisted methods aid Heidelberg physicists in reproducing experiment with ultracold atoms

Two researchers at Heidelberg University have developed a model system that enables a better understanding of the processes in a quantum-physical experiment...

Im Focus: Glacier bacteria’s contribution to carbon cycling

Glaciers might seem rather inhospitable environments. However, they are home to a diverse and vibrant microbial community. It’s becoming increasingly clear that they play a bigger role in the carbon cycle than previously thought.

A new study, now published in the journal Nature Geoscience, shows how microbial communities in melting glaciers contribute to the Earth’s carbon cycle, a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

New quantum liquid crystals may play role in future of computers

21.04.2017 | Physics and Astronomy

A promising target for kidney fibrosis

21.04.2017 | Health and Medicine

Light rays from a supernova bent by the curvature of space-time around a galaxy

21.04.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>