Advance of dengue virus stopped?

Protease inhibitor substance prevents virus multiplication successfully

12/10/2014

The dengue virus continues to spread globally. Especially children are threatened by the disease massively. Now protease inhibitors have been developed in the laboratory for the first time and have proven to be effective in the fight against HIV and hepatitis. The main focus of science in this context is the enzyme of the pathogen, the so-called protease NS2B / NS3.

Similar protease inhibitors have been around for some time. However, they were not effective enough, they only managed to reduce the virus multiplication by about 50 percent. The working group of the Würzburg virologist Jochen Bodem has now succeeded, in collaboration with scientists from the University of Mainz, to find far better inhibitors, which are now published in the journal „Antimicrobial Agents and Chemotherapy” to get presented. „We have developed seven good to very good inhibitors from the diaryl thioether molecular class, and two of them are actually really good“, says Bodem. Thus, the survival rate of the virus populations, even at low concentrations of the two drugs only at three percent. In addition, the protease inhibitors are very specific in their action and are directed exclusively against dengue viruses.

Mainly responsible for the development of the new active ingredients were a research group of the University of Mainz around Tanja Schirmeister and Hongmei Wu, as well as the research group of the University of Würzburg under the leadership of Jochen Bodem and his PhD student Stefanie Bock. As a next step, the scientists plan to check whether the new drugs have a negative effect on higher organs and whether they also there an inhibition of virus multiplication result.

Global spread of fever
Currently, dengue fever, which has its origins in tropical regions of the globe, is also spreading in other warm regions. Researchers see the cause of climate change and the associated spread of mosquitoes responsible for transmission. According to the Robert Koch Institute, there were already cases of dengue fever in southern France and Croatia in 2010. In 2013 there were 879 registered cases in Germany. Without exception, the patients had been infected with the virus in the risk zones. On a global scale, WHO estimated annual infections at approximately 390 million. The disease occurs today in about a hundred states, while in 1970 there were only nine.

Transmission of the virus by mosquitoes
The carriers of the virus are mosquitoes, especially the tiger mosquito. In most cases, around ninety percent, the infection remains symptom-free. However, if the disease breaks down, it manifests itself through flu-like symptoms that are life-threatening, especially in children. Without intensive care treatment, the mortality rate is around fifty percent.

There is currently no vaccine, as well as a therapy with specific drugs. Therefore, protection against mosquito bites, for example with appropriate creams to prevent bites, by mosquito nets and by clothing that covers the largest possible part of the skin, is particularly important and recommended. In this respect, the identification of the protease inhibitor „the first step in the development of a potential anti-dengue virus therapy“ as the researchers from Mainz and Würzburg in the journal Antimicrobial Agents and Chemotherapy expressed. (Jp)