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Ebola virus - everything you need to know

A complete guide to 2014 Ebola virus outbreak brought to you by Student Society of Molecular Biology at Faculty of Biology, University of Warsaw, Poland

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Transcript of Ebola virus - everything you need to know

Ebola Virus
A complete guide to 2014 Ebola virus outbreak
brought by the guests of KNBM

everything you need to know
http://newshour-tc.pbs.org
Virus structure and molecular properties
Outbreak and epidemiology
Pathogenesis, infection & symptoms
Vaccines and drugs
Aleksandra Fugińska | University of Warsaw
Magda Niedźwiedzka | Medical University of Warsaw
Łukasz Szymański | Military Institute of Hygiene and Epidemiology
Elżbieta Sokół | Centre of Postgraduate Medical Education
Introduction and essentials
group —V— viruses
anti-sense
single stranded
RNA
— morphologically —
filovirus
wikimedia.org
Ebola
virus
Marburg
virus
— classification —
Sudan
SUDV
Taï Forest
TAFV
Bundibugyo
BDBV
Reston
RESTV
zaire
ebov
ca. 80 nm in diameter and 800 nm in length
molecular structure
three major features
1. –ve ssRNA
2. rod-like capsid
3. viral membrane + GPs
cracking the code - ebola genome
through the cell - life cycle
http://www.bu.edu
capsid integrity
interferon blocking
membrane-bound or soluble
RNA stabilising
transcription machinery
replication
jessicasimien.com
in for the kill - cases of focus
nature.com
antiviral drugs - mabs of zmapp
trbimg.com
— ZMapp —
zmab + MB003

antibodies cocktail against EBOV-GP


administered after infection

24 or 48h
1 or 48h
with survival rate of
100 or 50% resp.
100 or 67% resp.
combined with INF alpha yields
100/75%
survival rate following administration after 3/4 days after infection
43%
survival rate of
following administration after confirmed viraemia and fever
— ZMapp optimisation —
chimerised Zmabs (m1H3, m2G4, m4G7
—>
c1H3, c2G4, c4G7)
screening and selection of best mixture (guinea pigs and non-human primates)
—>
Zmapp1 & Zmapp2

100% survival rate of 18 rhesus monkeys after administration of 3 doses (3/4/5 days after infection)
1st drug to be given to 7 Ebola sufferers during current epidemy
— Production —
nbcnews.com
Nicotiana bethamiana
Agrobacterium tumefaciens
magnION viral vector system
+
+
0.5g / kg
dry mass
5-8 days
easily scalable to
indastrial production
GMP compatible
good manufacturing practise
mammalian
pattern of
glycosylation
strategies for vaccines development
Choi and Croyle
cAd3-EBOV
produced by GSK and NIAID
100% efficacy in non-human primates
I phase testing in the USA and the UK
Kanapathipillai et al., 2014
rVSVΔG-EBOV-GP
produced by NewLink Genetics and PHAC
100% efficacy in non-human primates
I phase tests in the USA
Kanapathipillai et al., 2014
II phase tests
IIa in Africa non-affected by EVD
IIb in Ebola virus affected population
stepped-wedge model
Kanapathipillai et al., 2014
Choi and Croyle, 2014
ebola outbrakes timeline
2000
2003
2014
2007
1995
1976
430
250
250
250
160
5000
As of October 25th there have been
4922
deadly EVD cases
11x
more
than in the biggest outbreak
back in 1976
50%
of all
cases
giving Ebola virus mortality rate of 0.5,
which means out of 10 infected people,
5 will die if not treated
Where it all started
current outbreak in w africa
2014
liberia
3211 reported cases
Sierra leone
1938 reported cases
guinee
1021 reported cases
recently declared
ebola free
by WHO after the test period
of 42 days
ebola virus outside of africa
At least
18 people
reported with EVD
outside W Africa
Craig Spencer
Teresa ramos
doctor of medicine
treated at NYC Bellevue Hospital
brincidiofovir
auxillary nurse
cured of EVD
serum & antiviral drugs
preventive
health organisations response
international
american
european
// year of outbreak
// number of fatalities
why west africa?
pharmaceutical-journal.com
pharmaceutical-journal.com
evd pathogenesis and symptoms
overview
robust replication in cells
intense replication in macrophages causes
necrosis of major organs
liver
spleen
lymph nodes
lungs
lysis of endothelial cells in blood vessels leads to
broad internal and
external bleedings
soluble GPs released to the blood and bodily fluids
blocks antibodies activity
severe
haemorrhagic
fever
monocytes
macrophages
dendritic cells
disfunction of the host immune system
cytokine release
similar to sepsis
thus the name "haemorrhagic"
so the virus could evade immune system response
EVD symptoms
— fever —
— stomach ache —
— bloody diarrhea —
— skin rush —
— vomiting —
— muscle pain —
viral transmission
incubation period of
2 to 21 days
asymptomatic patiens are not infective
additional
factors of spread
males can spread ebola virus via semen up to 7 weeks after recovering from evd
non-hygienic
burial rituals of
african cultures
contraction via travellers without proper health care
preventive measures
infected individuals
must be isolated
special measures must be taken in order to provide healthcare for such individuals
healthy individuals being at risk should remain in
quarantine
i.e. people who have had contact with infectious individuals/animals
in hospitals, application of
detergents
and uv light
in cleaning procedures
infected animals
must be put down
pets included
diagnosis
ELISA
animal (cell) culture
RT-PCR
to obtain sufficient amounts
of viral material for further analyses
immunodetection set against viral antigens
genome-based method
small-molecule drugs
VP24 membrane-associated protein
L polymerase
VP35 polymerase complex protein
viral matrix protein
VP30 RNA binding protein
mammalian glycoprotein
nucleoprotein
Choi and Croyle, 2014
tkm-Ebola
set of siRNAs against L polymerase, VP24, VP35
January 2014: I phase clinical tests
July 2014: FDA ban due t side effects
August 2014: FDA change of status, approval for further tests
JK-05
designed by Chinease researchers
selective blocking of L polymerase
discovered 5 yrs ago and tested on animals ever since
positive outcomes on human trials, yet not approved for treatment
soon to be approved
BCX430
synthetic analogue of adenosine
broad spectrum of antiviral activity
incorporation of BCX430 - a monophosphate into elongated RNA, which blocks further elongation
FAVIPIRAVIR
experimental drug, broad range of antiviral activity
produced by Japanese company Toyama Chemical
L polymerase inhibition
September 19: administered to a French woman infected with EBOV
aka T-705 or Avigan
Full transcript