Monday, 7 December 2015

What are Chemists Doing to Fight Ebola?

By David Morris  

Since the beginning of 2014, Western Africa has been battling an outbreak of Ebola Haemorrhagic fever (EHF), or simply ‘Ebola’. The epidemic caused by the Ebola virus has been largely contained, but the death toll is still ascending into the tens of thousands. To understand what chemists have been doing to exterminate the virus, some background knowledge of it is required.

An electron micrograph of an Ebola virus 

The Ebola virus is a filamentous virus comprised of a strand of genetic code known as RNA, encapsulated by a protein membrane. It can survive in a multitude of bodily fluids for up to several months, making inter-host transmission very feasible. The fruit bat, native to parts of western Africa serves as a ‘natural reservoir’ for the virus. This means the virus can survive and replicate within a fruit bat without killing it, allowing it to thrive in countries where fruit bats are prevalent. RNA acts as a code for the expression of specific proteins. After the Ebola virus is introduced to the human body, it expresses a protein that binds to human ‘interferons’. These are proteins that call for an immune response when necessary. This binding stops the interferons calling for antibodies to destroy the virus, rendering the immune system largely redundant.
The exterior membrane of the virus presents pendant proteins called glycoproteins to the surface of a healthy cell. The Ebola glycoprotein hijacks the cholesterol influx receptors of healthy cells, dragging the virus into them. This allows the virus easy access to the cell interior, where it is free to replicate.
The Ebola virus also expresses a disordered protein called VP24 that interacts strongly with the collagen in the body. Collagen is responsible for separating connective tissues and acting as a barrier to prevent unwanted materials entering organs and tissues. When VP24 interacts with collagen, it can distort the collagen until the collagen is denatured and useless. After this, there is little else stopping blood pouring into organs and to the surface of the skin, thus widespread internal and external bleeding occurs and causes fatal problems in the body.
The many ways that the Ebola virus acts on the body has given chemists just as many platforms from which it can be stopped. Upon entering the body, the virus is very quick to shut down the immune system. The body tries to respond by expressing a specific antibody to combat the virus. Scientists have noticed this and developed an effective way to detect the rapid expression of this antibody, making early diagnosis and recovery from the disease much more likely.

Many contemporary EHF treatments are derived from molecules that are very structurally similar to what the virus uses in protein expression and replication. Sarepta Therapeutics have developed a modified strand of RNA that, when deployed, the virus encounters in the body and mistakes for its own genetic code during replication. Due to the modified code, the daughter virus then goes on to express dysfunctional VP24 which can’t bind to interferons properly, allowing them to signal the immune response to destroy the virus. Similarly, Tekmira Pharmaceuticals have developed ‘small interfering’ RNA drugs that the virus again mistakes for its own RNA. This modified RNA prevents the daughter virus from being able to replicate itself at all. Mapp Biopharmaceuticals developed ZMapp as a ‘cocktail’ of several antibodies that have a high affinity to Ebola glycoprotein. The cell doesn’t mistake the new glycoprotein-ZMapp structure for cholesterol upon binding and so isn’t tricked into allowing the virus into the cell. As the virus cannot infect new cells, it eventually perishes. These techniques have resulted in a plethora of antiviral drugs that can be used to treat EHF. Applying these remedies in conjunction with one another increases the likelihood of effective treatment exponentially as it stops the virus at several points.
These types of drugs work well as they are very structurally similar to the actual virus, such that they have a much higher affinity for the virus as opposed to human cells. This allows the drug to selectively interrupt the virus’ processes over bodily processes, and therefore limits the potential negative effects of the drug on the patient.
Chemists are currently developing methods for EHF drugs to be made in a quick, scalable and economically viable fashion with few toxic impurities, so they can pass through clinical trials and be used on scale. Ebola recovery is now becoming more and more common. With the research effort the pharmaceutical industry is pouring into fighting the Ebola virus, it is very realistic that the epidemic will be exterminated and effectively controlled within the coming years.