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.
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| 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.
