Distributed computing has helped to find a new cure for dengue fever

Maxim Malakhovsky, distributed.org.ua based on the materials of the World Community Grid: A new drug lead to combat dengue feverDr. Stan Watowich from the University of Texas Medical Branch (UTMB) in Galveston shares with numerous participants of the World Community Grid association the good news.

Scientists who attracted large computing capacities of volunteers from all over the world to the Discovering Dengue Drugs – Together project (the project "All together – to find a cure for dengue"), after years of research, were able to discover a very promising medicinal substance to combat a dangerous tropical disease – dengue fever.

People affected by dengue fever experience excruciating joint and muscle pain, high fever and headache during the illness. The severe form of the disease, known as hemorrhagic dengue fever, is one of the main causes of hospitalization and death among children in many Asian and Latin American countries. According to the World Health Organization (WHO), more than 40% of the world's population is at risk of dengue fever. According to some estimates, in 2010, about 390 million cases of dengue were associated with diseases in the world.

Mosquitoes are carriers of dengue infection, and the most critical epidemiological situation is observed in tropical and subtropical regions of developing countries in Africa and Latin America. Viruses that cause dengue fever belong to the flaviviruses (Latin Flaviviridae), a family of viruses that also include viruses that cause hepatitis C, West Nile fever and yellow fever.

Despite the critical danger of dengue fever on a global scale, this viral disease has not received close attention from the international research community until recently and is considered one of the forgotten tropical diseases. Currently, there are no approved vaccines or reliable treatments for this disease. Therefore, in 2007, researchers from Texas launched a project to search for promising drugs for dengue fever using computer screening of chemical compounds that can potentially neutralize the virus that causes this disease.

Thanks to the attracted computing resources, researchers from the University of Texas were able to analyze the features of the interaction of the virus with 3 million chemical compounds – potential drug molecules, which were required to show the ability to bind to the biomolecules of the virus and turn off its enzymes. By 2009, several thousand promising chemical compounds had already been found and it became possible to proceed to the next stage of testing. The strongest substances were selected from these compounds in order to further transform them into drugs that may be suitable for clinical trials on humans.

When additional calculations were performed on the web portal for advanced detection of drug molecules using the DrugDiscovery@TACC computer technology, an amazing discovery was made. One of the previously selected molecules demonstrated success in binding and disabling the key enzyme of the dengue virus responsible for the ability of the virus to replicate – the NS2B-NS3pro protease.

A drawing from an article in J. Chem. Inf. Model.

Moreover, the found molecule will probably also be able to effectively disable the enzymes of flaviviruses that cause West Nile fever. It is important to note that the discovered substance does not show any negative side effects - it is not toxic to the body, has low levels of carcinogenicity and mutagenicity. All this makes the substance a promising candidate for antiviral medicine against dengue and other flaviviruses.

Now researchers from the University of Texas are working with chemists to synthesize this candidate drug "in vitro" in order to increase its activity for the start of planned preclinical and clinical trials.

Dr. Stan Vatovich once again expresses his deep gratitude to all participants of distributed computing from the World Community Grid for their invaluable contribution to the discovery. He also hopes that the rest of the research that is currently underway within the framework of the association will also result in outstanding discoveries and will serve for the benefit of science and for the benefit of humanity.

Article by Viswanathan et al. Identification of a Novel Inhibitor of Dengue Virus Protease through Use of a Virtual Screening Drug Discovery Web Portal is published in the latest issue of the Journal of Chemical Information and Modeling.

Portal "Eternal youth" http://vechnayamolodost.ru09.12.2014