Researchers propose better substances for treating the dengue virus

December 10, 2014, Universitaet Mainz
Researchers propose better substances for treating the dengue virus
The interactions of the protease inhibitor (yellow) with the enzyme were analyzed using computer-assisted methods. Credit: Hongmei Wu

Researchers from Johannes Gutenberg University Mainz (JGU) and the Julius Maximilian University of Würzburg are proposing potential new active substances for treating the dengue virus. Just like Ebola, dengue fever is also caused by a virus for which there is currently no cure and no vaccine and can be fatal.

In the quest for medication to treat the , the scientific community is focusing on a particular enzyme of the pathogen, the protease known as NS2B/NS3. The reason for this is that inhibitors of similar proteases have been revealed to be very effective with other viruses. Protease inhibitors are already being used successfully in the treatment of HIV and Hepatitis patients. There are also several inhibitors for the dengue protease. However, at best, they stop only half of the viruses from multiplying, which is not enough for clinical applications. The Würzburg team led by virologist PD Dr. Jochen Bodem, in collaboration with scientists from Mainz University, has discovered far better inhibitors, which are now presented in the journal Antimicrobial Agents and Chemotherapy.

"We have developed seven good to very good inhibitors from the diaryl thioether class of molecules, and two of these are even really good," said Bodem. When these two are used, only around three percent of the virus population in a cell culture survives even with very low concentrations of the active substance. From the point of view of science, this is a very good result, especially as the inhibitors, as desired, are highly specialist: they only target dengue viruses and have no impact whatsoever on very close relatives like the Hepatitis C virus.

The new active substances were developed by a team of virologists and pharmacists. From Mainz, Professor Tanja Schirmeister and, in particular, her colleague Hongmei Wu, were involved. Schirmeister's team synthesized the inhibitors and then examined and further developed their interactions with the enzyme using computer-assisted methods. On Jochen Bodem's team, Stefanie Bock, who is now working towards a doctorate at the University of Münster, played a key role. Here the protease of the viruses was obtained and cleaned. The effect of the active substances on the dengue virus was later demonstrated in the safety laboratory. As a next step, the scientists will check whether the new active substances have negative effects on higher organisms and whether they inhibit viral replication there as well.

Dengue fever originated in the tropics. However, for a few years now it has also been found in other warm regions of the world, such as the Mediterranean. Scientists are attributing this to climate change: the mosquitoes that transmit the virus to humans are able to expand their habitat thanks to increasing global warming. Back in 2010, the Robert Koch Institute reported on in southern France and Croatia. In Germany in 2013, there were a total of 879 recorded dengue patients - all travelers who had become infected in the southern hemisphere and in tropical countries. The World Health Organization (WHO) estimates that the number of infections globally stands at 390 million a year. In 1970, infections occurred in just nine countries. These days, that figure has already risen to over 100.

The virus is transmitted by the tiger mosquito and other mosquitoes. Usually the infection goes unnoticed since there are no signs of the disease in almost 90 percent of cases. In the remaining cases, an influenza-type illness develops, which may take a potentially fatal course, especially in children. In addition to muscle and bone pain accompanied by a high temperature for days, the patient then develops internal bleeding and other severe symptoms. Without intensive medical treatment, around half of these sufferers die. To date, there is no vaccine and no way of fighting the virus with specific drugs. It is therefore recommended that measures be taken to protect against mosquito bites in countries where there is a risk of infection, such as covering the skin with clothes as much as possible, sleeping under a mosquito net, and applying mosquito-repellent creams.

Explore further: Targeting key cells for a dengue virus infection model

More information: H. Wu et al., Novel Dengue virus NS2B/NS3 protease Inhibitors, Antimicrobial Agents and Chemotherapy, 8 December 2014,
DOI: 10.1128/AAC.03543-14

Related Stories

Targeting key cells for a dengue virus infection model

November 5, 2014
Dengue virus infects hundreds of millions of people living in tropical countries every year. Transmitted via mosquito bites, the virus typically causes fever, but may also lead to potentially fatal organ failure. The development ...

New approach holds promise for dengue fever

December 2, 2014
Monash University and 60P Australia Pty Ltd (60P), a subsidiary of 60° Pharmaceuticals LLC, have announced today an exclusive partnering deal, with 60P obtaining rights to develop the drug Fenretinide for dengue fever.

Dengue mosquito hitched ride from southeast US to reach California

August 7, 2014
(Medical Xpress)—The mosquito that transmits Dengue Fever probably arrived in California by plane or railway from the southeastern United States—and not from Mexico—a DNA analysis by Yale University researchers has ...

Six die in dengue virus outbreak in southern China

October 7, 2014
The dengue virus has killed six people and infected more than 23,000 in southern China's worst outbreak of the mosquito-transmitted disease in about two decades, officials said Tuesday.

A gut bacterium that attacks dengue and malaria pathogens and their mosquito vectors

October 23, 2014
Just like those of humans, insect guts are full of microbes, and the microbiota can influence the insect's ability to transmit diseases. A study published on October 23rd in PLOS Pathogens reports that a bacterium isolated ...

Japan sees first local dengue case in over 60 years

August 27, 2014
Japanese health authorities have reported the first locally transmitted case of dengue fever in the country in more than 60 years.

Recommended for you

Ambitious global virome project could mark end of pandemic era

February 23, 2018
Rather than wait for viruses like Ebola, SARS and Zika to become outbreaks that force the world to react, a new global initiative seeks to proactively identify, prepare for and stop viral threats before they become pandemics.

Forecasting antibiotic resistance with a 'weather map' of local data

February 23, 2018
The resistance that infectious microbes have to antibiotics makes it difficult for physicians to confidently select the right drug to treat an infection. And that resistance is dynamic: It changes from year to year and varies ...

Scientists gain new insight on how antibodies interact with widespread respiratory virus

February 22, 2018
Scientists have found and characterized the activity of four antibodies produced by the human immune system that target an important protein found in respiratory syncytial virus (RSV), according to new research published ...

Study reveals how kidney disease happens

February 22, 2018
Monash researchers have solved a mystery, revealing how certain immune cells work together to instigate autoimmune kidney disease.

Past encounters with the flu shape vaccine response

February 20, 2018
New research on why the influenza vaccine was only modestly effective in recent years shows that immune history with the flu influences a person's response to the vaccine.

Building better tiny kidneys to test drugs and help people avoid dialysis

February 16, 2018
A free online kidney atlas built by USC researchers empowers stem cell scientists everywhere to generate more human-like tiny kidneys for testing new drugs and creating renal replacement therapies.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.