Outsmarting Ebola together

The Ebola virus, which is the cause of the worsening humanitarian catastrophe in Africa and threatens to spread across the territories of other countries, currently has no effective means for treatment and prevention.

Ebola virus in humans and animalsFirst identified in 1976, the Ebola virus is similar in structure to the Marburg, Sudan and Reston viruses, as well as other representatives of the filovirus family.

Only in 2014, one of the Ebola strains caused a serious epidemic in West Africa, another strain caused a smaller outbreak in the Democratic Republic of the Congo, and the Marburg virus claimed many lives in Uganda. In recent years, the Sudanese virus has caused many outbreaks in Central Africa, and the Reston virus has been detected in China and the Philippines on many farms that raise pigs for food production. It is believed that the natural reservoir of the Ebola virus are carnivorous bats; animals infected as a result of their bite can also be carriers of infection. The virus could have entered the territory of West Africa about 10 years ago as a result of the migration of bats or other animals, and in December 2013 it entered the human population, marking the beginning of the epidemic that continues to this day. 

At the beginning of November 2014, the total number of cases of Ebola infection in Guinea, Liberia and Sierra Leone alone approached 18,000, killing at least 5,000 people.

Here, the data on the number of cases and deaths from Ebola in 2014 are several months out of date – VM.

Symptoms of EbolaA particle of the Ebola virus, shaped like a long flexible fiber, attaches to the cell surface and penetrates into the intracellular space, where it quickly replicates, releasing a huge number of new copies of the virus from the cell.

The virus affects several types of cells, including important immune system cells that circulate in the circulatory system and spread the virus throughout the body. The damage caused by the virus includes inadequate thrombosis, the exudation of fluid from blood vessels into tissues, inflammation, the development of organ failure and shock. The incubation period from the moment of infection until the first symptoms appear lasts from 2 days to three weeks. The first symptoms may be similar to those of influenza or common tropical diseases, after which severe fever, vomiting, diarrhea, dehydration and other life-threatening manifestations develop. Depending on the strain and the intensity and adequacy of therapy, the disease leads to the death of patients in 25-90% of cases.

Contact with the biological fluids of an infected person or the body of a deceased person from the disease can lead to infection. Given the variability of the incubation period and the innocuousness of the first symptoms, to suppress the outbreak of morbidity, it is extremely important to track and isolate all people who have potentially come into contact with infected people.

The impact of the Ebola virus on the populationThe Ebola virus is potentially a very serious threat not only because of the severity of the disease, but also because of the fear it instills in people.

In the absence of a properly organized fight against the outbreak of the disease, it can develop into an epidemic and complicate the provision of medical care in the region, which will worsen the quality of treatment of other diseases and the provision of medical care to pregnant women. At the same time, industry and trade suffer and, accordingly, the welfare and the state of the economy of the region as a whole deteriorates. This situation is already being observed in some countries of West Africa, especially in Liberia and Sierra Leone. Due to the long incubation period and the close relationships between remote countries characteristic of the modern world, the Ebola virus can easily spread to other geographical regions. Therefore, the care of potential patients requires compliance with the strictest precautions, as well as the search for people who could come into contact with them.

Search for an effective treatment methodGiven the mortality rate, the scale of the 2014 outbreak and the possibility of the Ebola virus entering other territories, the search for an effective antiviral drug for its treatment is currently a very urgent task.

Several experimental drugs are showing promise and are currently undergoing urgent clinical trials. However, researchers are doing everything possible to find an unambiguously effective remedy, and there is still a lot of work in this direction.

Proposed solutionAs part of the Outsmart Ebola Together project, Ollmann Saphire Laboratory researchers from the Scripps Research Institute in La Jolla, California, are using the World Community Grid distributed computing platform to search for drugs to treat patients infected with the Ebola virus.

Effective drugs against this disease can potentially be used for the treatment of related diseases caused by pathogens of the filovirus family, including Marburg, Sudan and Reston viruses.

Computing power provided by World Community Grid volunteers is used to screen millions of compounds in order to identify molecules capable of disarming the Ebola virus. Virtual screening replaces many years of laboratory research.

Screening of potential therapeutic moleculesThe AutoDock and AutoDock VINA programs used for this screening were developed by the Arthur J. Olson Laboratory

 from the Scripps Research Institute, which also acted as a partner of World Community Grid during two other projects: FightAIDS@Home and GO Fight Against Malaria.

For more information about what RV is, see the article "Distributed Computing: Volunteers in the Service of science"; at the end of it, it describes how to join millions of volunteers around the world participating in dozens of projects in 5 minutes.

The program introduces information about the atomic structure of the Ebola virus particle and the structures of millions of potential therapeutic molecules – ligands (substances capable of binding to the target molecule, in most cases changing its properties). The target and ligands are compared with each other in all dimensions, after which the software evaluates the potential strength of the bonds formed between them. This process is a virtual simulation of what is happening in a laboratory test tube. It provides significant savings in time and money, since it is necessary to acquire or synthesize potential therapeutic molecules for laboratory testing.

Molecular targets of the Ebola virusThis project is being carried out with the support of the Allmann Sapphire Laboratory, which has provided unique data on the structural biology of the Ebola virus, including almost all critical target proteins of the viral particle.

The molecular images of the virus obtained by the researchers demonstrate its vulnerabilities, as well as regions, the impact on which can block key stages of the virus' life cycle. The laboratory also has the tools and skills to conduct a biological assessment of any potentially effective compound at each stage of the virus life cycle.

The first target will be the surface protein of the virus envelope, which ensures infection of human cells. The results recently obtained by the laboratory indicate that Ebola-related viruses use molecular structures of a similar shape to infect human cells. Based on the compounds binding in this structure, it is possible to develop drugs against any pathogen of the filovirus family.

The second target will be the newly identified "transformer proteins" of the Ebola virus, which change their shape depending on the functions performed.

Development of a drug for the treatment of the Ebola virusAfter the most promising compounds are selected using a virtual screening organized by the World Community Grid platform, they will undergo a laboratory test of effectiveness against a real viral infection.

The most promising of them will be modified to achieve maximum effectiveness at low dosages and reduce the risk of unwanted side effects. Subsequent clinical trials may lead to the emergence of effective drugs that have received official approval for use in the treatment of the Ebola virus.

The goals of the project "Outsmarting Ebola together":To screen millions of compounds from a variety of laboratory databases in search of molecules specific to critical target proteins of the Ebola virus particle.

• Identify the most promising candidate molecules and conduct further laboratory analysis in order to identify compounds with maximum efficiency.
• To provide the results to other researchers around the world working on the creation of means to combat the Ebola virus.

How to support the projectAnyone can help researchers in finding a cure for a deadly virus:

• provide unused computing power of your computer (this will not affect the operation of your programs at all),
• to attract other people to participate in the project,
• to participate in a crowdfunding campaign conducted by the Scripps Research Institute, which collects additional funds necessary for the analysis of a huge amount of data obtained within the framework of the project.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the World Community Grid: Let's outsmart Ebola together.

08.12.2014