Indo American Journal of Pharmaceutical Research, 2014

ISSN NO: 2231-6876

EBOLA VIRUS DISEASE: EPIDEMIC BROKE OUT IN LATERAL AFRICA

T.Naga Ravikiran1*, A.V.S.Madhulatha2, Y.Rajendra Prasad1
1

Dept of Pharmaceutical chemistry, AU college of Pharmaceutical sciences,Visakhapatnam. Andhra Pradesh, INDIA.

Krishna University college of Pharmaceutical sciences, Machilipatnam, Andhra Pradesh, INDIA.

ARTICLE INFO
Article history
Received 16/12/2014
Available online
31/12/2014

Keywords
Haemorrhage,
Transmission,
Dissemination,
Incubation,
Meningitis,
PCR Technique.

ABSTRACT
Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever), is a severe, often
fatal illness, with a case fatality rate of up to 90%. There are no licensed specific treatments
or vaccine available for use in people or animals. Genus Ebolavirus is 1 of 3 members of the
Filoviridae family (filovirus), along with genus Marburgvirus and genus Cuevavirus. Genus
Ebolavirus comprises 5 distinct species: Bundibugyo ebolavirus (BDBV), Zaire ebolavirus
(EBOV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV) and Ta Forest ebolavirus
(TAFV). The incubation period of Ebola virus disease (EVD) varies from 2 to 21 days, with
an observed average of 8 to 10 days. The most common symptoms experienced by persons
infected with the virus are the sudden onset of fever, intense weakness, muscle pain, headache
and sore throat followed by vomiting, diarrhea, rash, impaired kidney and liver function, and
at advanced stage, both internal and external bleeding. Laboratory findings include low white
blood cells and platelet counts and elevated liver enzymes. Currently, no specific licensed
therapy has demonstrated efficacy in the treatment of EVD.Nevertheless,a ray of hope
blooms in the aisle of exploration in the form of three drugs BCX 4430, Favipiravir,
Brincidofovir. PREVENTION IS MANIFOLD BETTER THAN CURE. Withstanding
and combating of mankind to this epidemic is dependent on purely the preventive steps
adapted and implemented stringently.

Copy right 2014 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Please cite this article in press as T.Naga Ravikiran et al. Ebola Virus Disease: Epidemic Broke out in Lateral Africa. Indo
American Journal of Pharm Research.2014:4(12).

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Corresponding author
T.Naga Ravikiran
Research Scholar,
Dept of Pharmaceutical Chemistry,
Andhra University College of Pharmaceutical Sciences,
Visakhapatnam,
ravikirannaga58@gmail.com ,
+91-8333870913.

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INTRODUCTION
Pivotal facts
Ebola virus disease (EVD),precedingly known as Ebola haemorrhagic fever, is a relentless, often catastrophic illness in
humans.
The virus is imparted to people from animals and escalates in the human race through direct transmission. The average
EVD case fatality rate is around 50%. Case fatality rates have varied from 25% to 90% in the former outbreaks. The first ever
EVD outbreaks tookplace in isolated villages in Central Africa, near tropical rainforests, but the most recent outbreak in west
Africa has involved major urban as well as rural areas.
Community awareness about the disastrous infection is key to successfully control the outbreaks. Good outbreak control
relies on applying a package of interventions namely case management, surveillance and contact tracing, a proximate laboratory
service, safe entombing and social mobilisation.
Early supportive care with rehydration, symptomatic treatment improves survival chances. There is as yet no licensed treatment
proven to neutralise the virus but a range of blood, immunological and drug therapies are under exploration.
There are currently no licensed Ebola vaccines but three potential candidates are undergoing evaluation.1,5
In the Past
Ebola virus disease (EVD) first appeared in 1976 in 2 simultaneous outbreaks, one in Nzara, Sudan, and the other in
Yambuku, Democratic Republic of Congo. The latter occurred in a village near the Ebola River, from which the disease takes its
name.
The current outbreak in west Africa, (first cases notified in March 2014), is the largest and most complex Ebola outbreak
since the Ebola virus was first discovered in 1976. There have been more cases and deaths in this outbreak than all others
combined. It has also spread between countries starting in Guinea then spreading across land borders to Sierra Leone and Liberia,
by air (travellers only) to Nigeria, and by land (travellers) to Senegal and also to USA. 3,7
Geographical Spread :
The most severely affected countries, Guinea, Sierra Leone and Liberia have very weak health systems, lacking human
and infrastructural resources, having only recently emerged from long periods of conflict and instability. On August 8, the WHO
Director-General declared this outbreak a Public Health Emergency of International Concern. 5

Dissemination:
It is thought that fruit bats of the Pteropodidae family are natural Ebola virus hosts. Ebola is induced into the human race
through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as chimpanzees, gorillas,
fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.

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Sub-types :
The virus family Filoviridae includes 3 genera: Cuevavirus, Marburgvirus, and Ebolavirus. There are 5 species that have
been identified: Zaire, Bundibugyo, Sudan, Reston and Ta Forest. The first 3, Bundibugyo ebolavirus, Zaire ebolavirus, and
Sudan ebolavirus have been associated with large outbreaks in Africa. The virus causing the 2014 west African outbreak belongs
to the Zaire species. 3

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Fig 1 Global spread of Ebola viral disease among certain parts of Africa and US.

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Ebola then spreads through human-to-human transmission via direct contact (through broken skin or mucous membranes) with the
blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing)
contaminated with these fluids. 4
Healthcare workers at risk :
Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has
occurred through close contact with patients when infection control precautions are not strictly practiced.
Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the
transmission of Ebola.
People remain infectious as long as their blood and body fluids, including semen and breast milk, contain the virus. Men
who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness
Incubation period :
The incubation period, that is, the time interval from infection with the virus to onset of symptoms is 2 to 21 days.
Humans are not infectious until they develop symptoms.
Lifecycle of Ebola virus :
The first major events in its life cycle involves Binding or Adhering to the plasma membrane of host cell,.It is followed
by the Macropinocytic uptake and interacting to Late Endosomes.The viral Glycoprotein cleavage is done thereafter by cysteine
proteases(also known as Thiolproteases hydrolyse proteins).Membrane fusion and nucleocapsid delivery concludes the Biological
clock of EVD. 6 They are thread-like in body and can be seen only under a Microscope.3,5
Filoviridae, of which Ebola virus is a member, is a family of viruses that contain single, linear, negative-sense ssRNA
genomes. The family name was derived from the Latin word filum, which alludes to the thread-like appearance of the virions when
viewed under an electron microscope.
The tubular Ebola virions are generally 80 nm in diameter and 800 nm long. In the center of the particle is the viral
nucleocapsid which consists of the helical ssRNA genome wrapped about the NP, VP35, VP30 and L proteins. This structure is
then surrounded by an outer viral envelope derived from the host cell membrane that is studded with 10 nm long viral glycoprotein
(GP) spikes.

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Fig-2 Life cycle of Ebola virus in its Host cell.

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Fig-3- Thread-like Structure of Ebola virus seen under Microscope.

Symptoms of EVD include Early (Fever, Nausea, Headache and tiredness) and Late (Vomiting,Diarrhoea,Coughing and
Bleeding) which lasts with Death.

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Fig-4 Symptoms of Ebola viral disease which precipitates with time.

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Symptoms :
First symptoms are the sudden onset of fever fatigue, muscle pain, headache and sore throat. This is followed by
vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding
(e.g. oozing from the gums, blood in the stools). Laboratory findings include low white blood cell and platelet counts and elevated
liver enzymes.4

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Diagnosis
It can be difficult to distinguish EVD from other infectious diseases such as malaria, typhoid fever and meningitis.
Confirmation that symptoms are caused by Ebola virus infection are made using the following investigations:
-Antibody-capture enzyme-linked immunosorbent assay (ELISA)
-Antigen-capture detection tests
-Serum neutralization test
-Reverse transcriptase polymerase chain reaction (RT-PCR) assay
-Electron microscopy
-Virus isolation by cell culture.
A number of tests can be used to diagonise Ebola within a few days of the onset of symptoms,which can detect the viruss
genetic material or the presence of Antibodies against the pathogen.
The most accurate of these is likely the polymerase chain reaction(PCR ) test,a technique.
Till date using PCR technique,Ebola viral disease is being diagonised,
Samples from patients are an extreme biohazard risk; laboratory testing on non-inactivated samples should be conducted under
maximum biological containment conditions.
Achilles heel of Ebola structure :

Fig-5 Lateral and Bottom view of Ebola virus.

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The crystal structure of Ebolavirus GP reveals a three-lobed chalice-like structure. The three GP1 subunits (colored blue
and green), mediate attachment to new host cells and are tethered together by the three GP2 subunits (white). GP2 forms the
protein machinery that drives fusion of the viral membrane with the host cell. The human antibody KZ52 (yellow) binds the GP at
the base of the chalice, where it bridges GP1 to GP2, before fusion of the membranes. 7

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Fig-6-Potential targets of Ebola virus and its structural features.

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Treatment and vaccines

Supportive care-rehydration with oral or intravenous fluids- and treatment of specific symptoms, improves survival.
There is as yet no proven treatment available for EVD. However, a range of potential treatments including blood products, immune
therapies and drug therapies are currently being evaluated. No licensed vaccines are available yet, but 2 potential vaccines are
undergoing human safety testing.

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In its biologically active form Ebolavirus GP contains two subunits with separate structural and functional roles.GP1 is
responsible for receptor engagement,while GP2 mediates fusion of viral and host membranes.The crystal structure showed that the
450-kDa GP is a trimer shaped like a three-lobed chalice with the bowl of the chalice formed by three GP1 subunits and the stem
of the chalice fashioned from three GP2 subunits that cradle and encircle the GP1 trimer. Here portions of the GP2 ( the internal
fusion loop and hepted repeat region ) together wrap around GP1, and in turn, hydrophobic residues of GP1 clamp the hepted
repeat of GP2 into its metastable, pre-fusion conformation. This clamp is released upon entry into the host cell through an as-yet
unidentified process, allowing GP2 to spring into its more stable, six-helix bundle conformation and trigger fusion of virus and
host membranes.
A team of researchers from the Scripps Research Institute,USA using diffraction data collected at ALS Beamline 5.0.2,
has recently determines the crystal structure of an oligomeric glycoprotein from the viral surface in complex with a rare antibody
derived from a human survivor. This work explains how the glycoprotein,termed GP,mediated recognition of the host cell,drives
fusion of the viral and host membranes (necessary for the viral entry into the host), and masks itself from immune surveillance.
The structure also explains why antibodies that neutralize the virus from immune surveillance.The structure also explains why
antibodies that neutralize the virus are so rare, identifies the very few sites to which a neutralizing antibody might bind, and thus,
provides templates for vaccines and antibodies against the virus.

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PROBABLE DRUG CANDIDATES till date.

1) BCX 4430
It is developed by BioCryst Pharmaceuticals with the funding of NIAID(National Institute of Allergy and Infectious
Diseases,Maryland)originally intended for the treatment of Hepatitis-C. It also shows broad-spectrum antiviral effectiveness
against a range of other RNAvirus families,including bunviruses,arenaviruses,paramyxoviruses.coronaviruses and flaviviruses.
BCX4430 has been demonstrated to protect against both Ebola and Marburg viruses in both rodents and monkeys, even
when administered up to 48 hours after infection 9

2) FAVIPIRAVIR
A pyrazinecarboxamide derivative T-705 (favipiravir) was evaluated against Zaire Ebola virus (EBOV) in vitro and in
vivo. T-705 suppressed replication of Zaire EBOV in cell culture by 4log units with an IC90 of 110M. Mice lacking the type I
interferon receptor (IFNAR(-)(/)(-)) were used as in vivo model for Zaire EBOV-induced disease. 9

BRINCIDOFOVIR

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Cidofovir
Brincidofovir is a modified version of an antiviral drug called cidofovir, which inhibits replication of a variety of DNA
viruses including poxviruses and herpesviruses. When cidofovir enters a cell, two phosphates are added to the compound by a
cellular enzyme, producing cidofovir diphosphate. Cidofovir is used by viral DNA polymerases because it looks very much like a
normal building block of DNA, cytidine. For reasons that are not known, incorporation of phosphorylated cidofovir causes
inefficient viral DNA synthesis. As a result, viral replication is inhibited. 9

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Prevention and control

Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact
tracing, a good laboratory service, safe burials and social mobilisation. Community engagement is key to successfully controlling
outbreaks. Raising awareness of risk factors for Ebola infection and protective measures that individuals can take is an effective
way to reduce human transmission. Risk reduction messaging should focus on several factors:
1)
Reducing the risk of wildlife-to-human transmission from contact with infected fruit bats or monkeys/apes and the
consumption of their raw meat. Animals should be handled with gloves and other appropriate protective clothing. Animal products
(blood and meat) should be thoroughly cooked before consumption.
2)
Reducing the risk of human-to-human transmission from direct or close contact with people with Ebola symptoms,
particularly with their bodily fluids. Gloves and appropriate personal protective equipment should be worn when taking care of ill
patients at home. Regular hand washing is required after visiting patients in hospital, as well as after taking care of patients at
home.
3)
Outbreak containment measures including prompt and safe burial of the dead, identifying people who may have been
in contact with someone infected with Ebola, monitoring the health of contacts for 21 days, the importance of separating the
healthy from the sick to prevent further spread, the importance of good hygiene and maintaining a clean environment.
HEROES IN THE SERVICE :
Doctors Samuel Brisbane, from Liberia, and Dr Sheikh Umar Khan from Sierra Leone both died after contracting the
Ebola virus infested patients who visited their clinics. 10
Dr Samuel Brisbane, 74, died from the Ebola virus on 26 July after contracting it from treating infected patients at the
John F. Kennedy (JFK) Medical Center in Sinkor, a district of the Liberian capital Monrovia. Brisbane was one of the countrys
top doctors and medical teachers, and over a long and distinguished career trained hundreds of Liberian students. Brisbane served
as a general practitioner for years before going on to run the Firestone Medical Center from 1992-2003. Later he was appointed
chief medical doctor at the JFK Medical Center. Brisbane was buried on his farm on the outskirts of Monrovia the day he died.
Dr. Sam Brisbane was a Liberian doctor, and he died from Ebola, a horrible, nightmarish disease. spent a considerable portion of
his career at the Firestone Medical Center where, from 1992 to 2003, he served as medical director. He later transferred to the
John F. Kennedy Medical Center (JFK), where he rendered services based on his nearly a half century of experience as a general
practitioner.

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Fig -7-Gallants who endured to death in serving the Ebolised patients.

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Infection in Health-care personnel :

Fig 8-Safety measures to avoid dissemination of Ebola viral disease.

Health-care workers should always take standard precautions when caring for patients, regardless of their presumed
diagnosis. These include basic hand hygiene, respiratory hygiene, use of personal protective equipment (to block splashes or other
contact with infected materials), safe injection practices and safe burial practices.
Health-care workers caring for patients with suspected or confirmed Ebola virus should apply extra infection control measures to
prevent contact with the patients blood and body fluids and contaminated surfaces or materials such as clothing and bedding.
When in close contact (within 1 metre) of patients with EBV, health-care workers should wear face protection (a face shield or a
medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures). 8
Laboratory workers are also at risk. Samples taken from humans and animals for investigation of Ebola infection should
be handled by trained staff and processed in suitably equipped laboratories.
The major hurdles observed in the path :
Lack of well developed research centres in those countries
Ebola virus rapid and expedite spread
Most expensive diagnosis of around $100 for single test
Delayed reports nearly 6 hours to test using PCR technique.
CONCLUSION
Even though,no drug seems to be a potent candidate to resist the massacre of the epidemic,some candidates tend to prove
life-saving. Community awareness about the outbroke is the only remedy for preclusion of the spread. W.H.O besides check book
diplomacy has to emerge as a path finder to this genocide. The death toll from the current Ebola outbreak has reached 756512.
Researchers relentless exploration to decipher promising drugs like BCX 4430,Favipiravir and Brincidofovir is under
evolution.

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Authors Statements
Competing Interests
The authors declare no conflict of interest.

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8. http://www.dhses.ny.gov/oem/safety-info/ebola/responders.cfm
9. www.cen.acs.org
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11. http://jis.gov.jm/features/ebola-virus-diseases-evd-implication-introduction-americas/
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