Schistosomiasis is a tropical disease caused by parasitic worms, which kills as many as 200,000 people per year and affects over 207 million people in 74 countries. To date, there are no available vaccines to prevent the disease, despite extensive research. Schistosomiasis is second only to malaria in its socioeconomic devastation.
The disease is caused by parasitic trematode worms (genus Schistosoma). The parasite's larvae, released by freshwater snails, penetrate the skin and eventually travel to the liver via the blood stream. Feeding on the host's blood, the parasites mature and move through the veins to other parts of the body such as the bladder and intestines. During their lifetime, which can be decades, they can produce hundreds of eggs per day. Some of the eggs are excreted in urine or feces, then hatch and infect more snails.
The body's immune response to the eggs, which remain in the body, is the main cause of the disease. The immune response is the body's natural defense mechanism to foreign invaders and normally causes temporary inflammation of the affected tissues. However, the disease causes continued inflammation, which damages the affected organs and so the problem becomes more severe. Schistosomiasis can affect various organs such as the liver, spleen, intestine, and kidneys, and can lead to death. One species of Schistosoma can also cause bladder cancer.
Antimony, oxamniquine, mirazid, and metrifonate are drugs that have been used to treat schistosomiasis, but these drugs are either not highly effective, have been discontinued, or work against only certain forms of the disease. An orally administered drug called praziquantel is currently the best treatment for schistosomiasis. However, there is evidence that Schistosoma may become resistant to praziquantel. For these reasons, there is an urgent need to develop new treatments.
To accelerate the search for potential drugs against schistosomiasis, the computing power of World Community Grid will be used to screen millions of potential chemical compounds as possible drug treatment candidates. Instead of performing expensive and time-consuming laboratory experiments, simulations of these millions of experiments will be performed using software running on World Community Grid's member computers.
A software program called VINA from The Scripps Research Institute in La Jolla, California, will be used to perform the virtual chemistry experiments, more precisely known as molecular dockings. Molecular docking is the process of determining how well two chemical compounds bind together. One of the chemical compounds is designated as the target, in this case one of several proteins essential for the parasite's survival. The other compound is one from a collection of millions of compounds from various databases, cataloging known compounds and their exact atomic structure. The docking experiments position the two compounds in all possible orientations, computing the binding energy for each, which tells how well they stick together in that configuration. If a compound binds to the target protein, it may be useful in disabling the function of that protein and thus the progress of the disease. The researchers are identifying Schistosoma proteins to be used for the project and are determining the atomic structure of those proteins so they can be used as targets for the molecular docking experiments.
The VINA calculations will be used to identify the most promising chemical compounds that may inhibit these proteins. The computations involved are very intensive and would take over 30 years to complete using computers normally available to the researchers. World Community Grid will be able to reduce the time required to test the millions of compounds against these proteins to one year or less. Information about the best candidate compounds will be published by the scientists, and this information will be placed in the public domain for other scientists to build upon with their research. The research team plans to conduct additional laboratory work using the best candidates identified by the VINA computations, which could lead to the development of better drugs to fight schistosomiasis.
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