Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An old new weapon against emerging Chikungunya virus

12.05.2016

Researchers utilize existing drugs to interfere with host factors required for replication of Chikungunya virus

Since 2013, the mosquito-borne Chikungunya virus has spread rapidly through South America and the Caribbean, and is now threatening Southern Europe and the southern US. It causes flu-like symptoms with fever and joint pains, which in some cases can last for months with occasional fatalities.


Chikungunya virus (yellow)

© Pasteur Institute/T. Couderc and M. Lecuit

No treatment or vaccine exists so far - serving as an urgent reminder of just how poorly the time-consuming process of drug development is able to meet the threat posed by newly emerging viruses.

Scientists at the Max Planck Institute for Infection Biology in Berlin have now teamed up with colleagues at the Paris-based Institut Pasteur to validate a new approach in the quest for a therapy – combining high-throughput screening for host cell proteins without which the virus cannot replicate, with so-called ‘drug repositioning’, i.e. utilizing an existing drug for new indications. They identified two existing compounds that were effective against the virus in an animal model. Their findings not only bring a Chikungunya treatment within potential reach, but also provide the proof of principle that this approach can be rapidly successful for newly emerging infectious diseases.

The recent Ebola and Zika outbreaks have highlighted how quickly new epidemics can spread in the age of global travel and how helpless modern medicine still is when faced with infectious diseases for which no treatment has been generated.

A case in point is Chikungunya fever, which has caused a rising epidemic since it first spread to the Caribbean and Latin America, with more than a million reported cases, and is now poised to spread into the US. While the symptoms are frequently mild, some patients experience crippling arthritic pain that can last for years.

Standard drug development procedures are both expensive and time consuming and the success rates are low. However, emerging epidemics require fast reaction. Professor Thomas F. Meyer with his group at the Max Planck Institute for Infection Biology have now pioneered a new strategy to achieve faster success: In a first step the overall requirement of host factors involved in the infection are identified and then, in a second phase, known drugs effective against the identified host factors are used to block the infection. This rational drug-repositioning strategy could speed up the development process dramatically and allow fast proof of concept.

The principle behind the rational drug-repositioning strategy is the emerging concept that all pathogens depend on proteins produced by the host cell in order to replicate successfully. The challenge lies in the identification of such critical host cell targets. The team found more than 100 host proteins to be required by Chikungunya, by using a robotic system at the MPIIB to knock out each human gene in turn, before infecting the cells with the virus and analysing how well it was able to replicate.

Together with the Marc Lecuit's group at Institut Pasteur, who are leading experts on the disease, and collaborators at the Steinbeis Innovation Center and the Charité in Berlin, the University of München and the Institute of Technology in Tartu, Estonia, they next searched for established compounds known to target the most promising host factors before testing them in vitro and in animal models of Chikungunya infection. This process resulted in two drugs, one of them an already widely used antipsychotic, which exhibit therapeutic activity in mice at safe doses, especially when used in combination. Further studies are now required to develop an optimized clinical therapy.

Excitingly, the results also revealed another potential benefit: ‘When we compared the requirement for every human gene in multiple unrelated viruses’ explains Dr Alexander Karlas, a leading virologist at MPIIB. ‘We found that several of the host proteins required by the Chikungunya virus are also required by several other, unrelated viruses as well.’ This potentially opens up a path for developing a range of broadly acting antivirals – which may give a much-needed boost in the battle against emerging viruses.

Contact

Prof. Dr. Thomas F. Meyer
Phone:+49 30 28460-400Fax:+49 30 28460-401
 

Dr. Rike Zietlow

Max Planck Institute for Infection Biology, Berlin

Phone:+49 30 28460-461

Original publication

Karlas, A., Berre, B., Couderc, T., Varjak, M., Braun, P., Meyer, M., Gangneux, N., Karo-Astover, L., Weege, F., Raftery, M., Schönrich, G., Klemm, U., Wurzlbauer, A, Bracher, F., Merits, A., Meyer, T.F. and Lecuit, M
A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

Prof. Dr. Thomas F. Meyer | Max Planck Institute for Infection Biology, Berlin
Further information:
https://www.mpg.de/10500598/chikungunya?filter_order=L&research_topic=

Further reports about: Biology Chikungunya Infection Max Planck Institute drugs

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>