First Steps Towards Controlling Deadly Ebola Virus

Mar 6, 2012 | Katharina Schwan | Outbreak News

New research suggests that certain cancer drugs may control ­the lethal Ebola virus. On February 29, a new study investigating the effects of two leukemia drugs on Ebola virus replication was published in the journal Science Translational Medicine.

The drugs, nolitinib and imatinib, sold by Novartis and marketed as Tasigna and Gleevec, are two types of tyrosine kinase inhibitors. Tyrosine kinase is an enzyme essential for the Ebola virus’ ability to replicate and spread throughout the body. The enzyme transports phosphates onto amino acids, which are the building blocks of proteins. This in turn affects the entire protein’s shape and function. The inhibitor impedes the transport of these phosphates, thereby halting the protein’s activity.

These drugs halt cancerous tumors in the same way. They prevent tyrosine kinase from completing the critical step of cell reproduction. By preventing reproduction, the drugs actually promote apoptosis (regulated cell death) and may ultimately halt tumor growth and potentially reduce tumor size.

This discovery on the Ebola virus is profound. A virus is a parasite, which means that it requires a host cell to replicate and reproduce its genes. By stopping the viral transport protein VP40 from releasing viral particles, the virus cannot spread through the body to infect new cells.  In order words, new copies of the virus are contained within their host cells. This provides the body’s immune system with enough time to control the infection before it spreads and becomes fatal. 

 

First Case of Ebola

Ebola hemorrhagic fever was first recognized during an outbreak in the Republic of Zaire, now the Democratic Republic of Congo. On August 28, 1976 a 44-year-old male entered the Yambuku Catholic Mission (YHM) in the Bumba zone of northern Zaire, complaining of a high fever. He was treated for malaria with an injection of chloroquine. The course of treatment was initially effective, however within three days, his fever returned and other symptoms began to emerge, including gastrointestinal bleeding. The patient died in the hospital on September 8.

Within the same month, YHM was forced to close because 11 out of its 17 staff members had succumbed to the same deadly infection. The disease spread to 55 villages in the surrounding area, infecting 318 individuals, 280 of whom died by the end of October.

Investigations revealed that YMH was the major source of dissemination of Ebola. Every morning the nursing staff received five syringes and needles to be used in the outpatient department, the prenatal clinic, and the inpatient wards. It was common practice to merely wash the needles in warm water. At the end of the day, they were sometimes boiled.

These poor sterilization procedures were directly linked to the spread of Ebola virus by parenteral injection. Direct contact with infected blood or secretions was a secondary mode of transmission, usually seen in patients’ close family members. 

Since the first outbreak in Zaire, a number of other outbreaks have occurred throughout Africa, such as in Sudan, Uganda, and Cote D’Ivoire. Overall, roughly 1850 Ebola cases have occurred, and 1200 deaths have been documented.

Ebola hemorrhagic fever is an extremely virulent and deadly disease that affects both humans and nonhuman primates, such as monkeys, gorillas, and chimpanzees. Certain outbreaks have had case fatality rates as high as 90 percent. Symptoms of Ebola include sudden fever, weakness, muscle pain, and sore throat. More extreme symptoms, such as vomiting, diarrhea, rash, impaired kidney and live function, as well as internal and external bleeding, may occur. Patients infected with the virus usually die within several days of presenting symptoms. No cure for Ebola has yet been invented.

 

Vaccine progress

In December 2011 a promising new trial for an Ebola vaccine ascertained its ability to protect against infection in mice. The results were published in the journal Proceedings of National Academy of Sciences. Charles Arntzen at Arizona State University is one of the lead investigators of the study. He determined that 80 percent of mice that received four vaccinations over a two-month period, survived after being infected with Ebola virus.

Although previously developed Ebola vaccines exist, their effectiveness deteriorates over time, as the viral particles in the vaccine become damaged after long-term storage. This new vaccine contains an artificial version of the virus that remains viable during longer storage processes.  This discovery also offers the possibilities for stockpiling, in case of potential large-scale outbreaks in the future.

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