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Research: Outsmart Ebola Together: Project Details Collapse   Expand  
 
About the Project

 

You can help researchers at The Scripps Research Institute find a cure for Ebola by donating your computing power to this project and encouraging others to join.



You can also support the research team by contributing to The Scripps Research Institute's crowdfunding campaign. The team will use these funds to analyze the enormous volume of data generated by Outsmart Ebola Together and study the most promising drug candidates.


The Problem

The Ebola virus is a significant health threat and is causing a growing humanitarian crisis in Africa, with potential to spread further due to human travel or expansion of the natural reservoir of animal hosts. It is a disease that kills 25% to 90% of infected victims and spreads human-to-human, often when patients are cared for or buried.

Currently, there are no proven treatments or vaccines for the disease. Although some have proposed using drugs developed for other viruses to attempt to fight Ebola, these drugs were designed to function against molecules that don't exist in Ebola and it is unclear if these treatments will be helpful. A better course of action is to leverage the wealth of scientific information that already exists for the Ebola virus to develop new, specific drugs. The molecular structures of Ebola virus's most important molecules have recently been solved, and represent rich, untapped opportunities for developing much-needed cures to fight this and future epidemics.

Ebola in humans and animals
The Ebola virus was first identified in 1976 and is closely related to the Marburg, Sudan and Reston viruses and other members of the filovirus family. In 2014 alone, one strain of Ebola virus caused the major outbreak in West Africa, a different strain of Ebola virus caused a separate, smaller outbreak in the Democratic Republic of the Congo, and the Marburg virus killed people in Uganda. The Sudan virus has caused multiple outbreaks over the years in Central Africa, and the Reston virus has been identified in China and the Philippines on multiple ranches of swine being raised for human consumption. Fruit bats are thought to act as the natural reservoir of the Ebola virus; other animals become infected as well. In West Aftrica, spillover into the human population in December 2013 triggered the current major outbreak. As of November 2014, Ebola virus has infected over 14,000 people and killed at least 5,000 in West Africa.



Symptoms of Ebola
The virus, which is shaped like a long, flexible filament, attaches to and drives itself into the cells of a host organism. It then replicates efficiently, budding out numerous copies of itself from the cell. The virus attacks several types of cells, including important cells of the immune system that circulate and carry the virus throughout the body. The result includes inappropriate clotting, leakage from blood vessels, inflammation, organ failure and shock. When a person is first infected, there is a two- to 21-day incubation period before the infected person shows symptoms. Initial symptoms, which closely resemble those caused by flu or common tropical diseases, progress to include high fever, vomiting, diarrhea, dehydration and more. Infection occurs by contact with an infected person's bodily fluids or the body of a patient who died from the disease. Because of the variable incubation period, and the similarity of initial symptoms to much more mundane diseases, it is important to track and isolate all possible contacts of an infected person to contain an outbreak.

Impact of Ebola on communities
Ebola is potentially a very serious threat, not only because of the severity of the disease itself, but also because of the fear it instills in a community. If not handled properly, an outbreak can turn into an epidemic and overwhelm the health services in a given area. Trade is also interrupted, and the entire welfare and economy of a region can deteriorate. This is already happening in some West African countries, particularly Liberia and Sierra Leone. Because of the long incubation period and our highly connected modern world, Ebola can easily spread into other regions after an initial outbreak. Extreme precautions and preparation are required in handling suspected patients and finding possible contacts who may also be infected.

The search for a cure
The search for an effective antiviral drug to treat the disease is now a high priority, given the mortality rate, the scope of the 2014 outbreak and the possibility that the virus could become endemic in one or more areas. Some compounds show promise as treatments for Ebola and are currently being tested through fast-tracked studies. However, scientists are still looking urgently for a definitive cure, and more must be done.

The Proposed Solution

In this project, researchers in the Ollmann Saphire laboratory of The Scripps Research Institute in La Jolla, California are using World Community Grid to search for drugs to treat patients infected with the Ebola virus. An antiviral treatment for Ebola could potentially also be used to treat related diseases in the filovirus family, including the Marburg, Sudan and Reston viruses.

The computational power donated by World Community Grid volunteers is being used to screen millions of compounds to identify those that show promise in disabling the Ebola virus. Performing this screening virtually saves many years of laboratory work.

Screening candidate drug molecules
The software used for these screenings is called AutoDock and AutoDock VINA, developed by the Olson laboratory at The Scripps Research Institute, which has also partnered with World Community Grid on two other projects: FightAIDS@Home and GO Fight Against Malaria.

The atomic structure of the target Ebola virus molecule and the structures of millions of candidate drug molecules (ligands) are inputs to the program. The target and ligand are evaluated in all orientations against one another, and the software computes the binding affinity between the molecules. This is analogous to what would be done in laboratory test tubes, but it is simulated virtually using computers. This saves considerable time and cost, because laboratory testing requires purchasing or synthesizing the candidate molecules, a potentially time-consuming and expensive process.

Ebola virus molecule targets
This project is aided by the unique expertise in Ebola virus structural biology in the Ollmann Saphire laboratory at The Scripps Research Institute. This lab has solved the structures of critical target proteins of the virus. These structures, or molecular images, are like reconnaissance: they show where the virus is vulnerable, and which specific sites should be hit to block key stages of the virus life cycle. The lab also has the tools and ability to biologically evaluate each compound at each stage of the virus life cycle in different cellular assays.

The first target will be the surface protein on the Ebola virus that is solely responsible for infection of new human cells. Recent work from this lab demonstrates that Ebola and its relatives, the Sudan, Marburg and Reston viruses, use a similarly shaped site to infect human cells. Compounds developed against this site could be developed into drugs against any of this family of viruses.

The second target will be newly discovered shape-shifting "transformer" proteins of the Ebola virus, which adopt different forms at different times to achieve different functions. With this project, we have the opportunity to make fundamental insights into molecular biology in general, understanding how the proteins of Ebola, and those of human cells as well, may leverage minimal genetic code into maximum biological function.

Developing a treatment for Ebola
Once the best candidate drug molecules have been identified through virtual screening on World Community Grid, they can then be tested in the lab. The most promising drug candidates can then be further modified to perform even better, at lower concentrations and with fewer side effects. Drug trials with the most promising drug candidates could ultimately lead to an approved medicine.

Project Goals

The goals of the Outsmart Ebola Together project are to:

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Screen millions of compounds from multiple library databases against critical Ebola virus targets.

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Identify the best candidates and perform further laboratory tests to identify promising drug leads for effective Ebola treatment.

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Provide the results to other scientists around the world who are working to fight Ebola.



The information on this page was last updated in December 2014.