Background:
Viperidae
snakes
are
responsible
for
many
of
the
94,000
deaths
caused
by
snakebite
envenoming
each
year.
The
most
pathological
venom
component
this
globally
diverse
family
zinc-dependent
snake
metalloproteinase
(SVMP)
enzymes,
which
can
be
inhibited
metal
chelator,
unithiol.
A
short-course
oral
regimen,
readily
available
and
rapidly
deployed
ahead
hospital
admission
is
needed.
Methods:
This
open-label,
phase
1
clinical
trial
assessed
safety
single
ascending
oral,
multiple
intravenous
doses
unithiol
in
64
healthy
adult
volunteers
from
Kilifi
County,
Kenya.
dose
stage
was
informed
an
interim
pharmacokinetic
analysis,
predefined
target
plasma
concentrations.
Plasma
concentrations
were
measured
using
high-performance
liquid
chromatography-mass
spectrometry,
described
full
adverse
event
reporting.
Findings:
175
individuals
screened,
(median
age
30
years,
IQR
25-38
years)
received
study
drug.
There
no
limiting
toxicities
or
serious
events.
61
solicited
events,
17
related
unsolicited
53
laboratory
all
mild
moderate
severity.
maximum
1,500
mg
well
tolerated
demonstrated
a
Cmax
that
equivalent
to
administration.
Interpretation:
2
recommended
(1,500
loading
dose,
followed
900
at
6-hours
24-hours)
safe,
has
promising
properties
use.
Unithiol
affordable,
stable
room
temperature,
potential
given
orally
remote
rural
clinics.
Its
further
development
indication
warranted.
Trial
Registration:
registered
on
Pan
African
Clinical
Trials
Registry
(PACTR202103718625048)Funding:
Wellcome
Trust,
Bloomsbury
Set,
Cures
Within
Reach.Declaration
Interest:
competing
interests
study.Ethical
Approval:
obtained
ethical
approval
Kenya
Medical
Research
Institute
Scientific
Ethics
Review
Unit
(192/4106)
Liverpool
School
Tropical
Medicine
Committee
(20-032),
regulatory
Pharmacy
Poisons
Board
(136).
conducted
accordance
with
requirements,
including
International
Conference
Harmonisation-Good
Practice
guidelines.
Transactions of the Royal Society of Tropical Medicine and Hygiene,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 3, 2025
Abstract
Haemotoxicity
is
the
most
common
complication
of
systemic
envenoming
following
snakebite,
leading
to
diverse
clinical
syndromes
ranging
from
haemorrhagic
prothrombotic
manifestations.
Key
haematological
abnormalities
include
platelet
dysfunction,
venom-induced
consumption
coagulopathy,
anticoagulant
coagulopathy
and
organ-threatening
thrombotic
microangiopathy.
Diagnostic
methods
bedside
whole
blood
clotting
test,
laboratory
coagulation
screening
other
advanced
such
as
thromboelastogram
clot
strength
analysis.
The
primary
management
strategies
are
venom
neutralisation
with
antivenom
correction
component
transfusions,
while
options
plasma
exchange
utilised
in
certain
cases.
Recent
advancements
understanding
pathogenesis
haemotoxicity
have
facilitated
development
new
diagnostic
treatment
modalities.
This
review
summarises
current
knowledge
on
pathogenesis,
diagnosis,
manifestations
effects
snake
envenoming.
Furthermore,
it
highlights
important
challenges
concerning
diagnosis
management.
Addressing
these
crucial
for
achieving
WHO's
goal
reducing
deaths
disabilities
caused
by
snakebites
2030.
Toxins,
Journal Year:
2025,
Volume and Issue:
17(3), P. 136 - 136
Published: March 14, 2025
Active
compounds
from
natural
sources,
particularly
snake
venoms,
are
crucial
for
pharmaceutical
development
despite
challenges
in
drug
discovery.
Snake
historically
used
medicinal
purposes,
contain
bioactive
peptides
and
enzymes
that
show
therapeutic
potential
conditions
such
as
arthritis,
asthma,
cancer,
chronic
pain,
infections
cardiovascular
diseases.
The
objective
of
this
study
was
to
examine
pharmacological
biomedical
innovations
by
identifying
the
key
research
trends,
most
studied
species,
their
applications.
A
systematic
review
patents
related
venoms
conducted
using
European
Patent
Office
database,
Espacenet,
covering
2014
mid-2024.
search
employed
keyword
“venom,”
applying
IPC
classification
A61K38/00,
resulting
31
after
screening.
PubMed
survey
on
“snake
venom
derivatives
innovations”
compare
scientific
literature
volume
with
identified
patents.
This
highlights
venom-derived
products
coagulation
disorders,
inflammation,
pain
management.
Despite
pharmacokinetics
variability,
advancements
biotechnology
offer
promise
personalized
therapies.
future
venom-based
treatments
appears
promising
addressing
complex
medical
conditions.
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
14
Published: Jan. 11, 2024
Snakebite
envenoming
is
a
neglected
tropical
disease
that
causes
as
many
1.8
million
envenomings
and
140,000
deaths
annually.
To
address
treatment
limitations
exist
with
current
antivenoms,
the
search
for
small
molecule
drug-based
inhibitors
can
be
administered
early
interventions
has
recently
gained
traction.
Snake
venoms
are
complex
mixtures
of
proteins,
peptides
molecules
their
composition
varies
substantially
between
within
snake
species.
The
phospholipases
A2
(PLA
2
)
one
main
pathogenic
toxin
classes
found
in
medically
important
viper
elapid
venoms,
yet
varespladib,
drug
originally
developed
acute
coronary
syndrome,
remains
only
PLA
inhibitor
shown
to
effectively
neutralise
venom
toxicity
vitro
vivo
,
resulting
an
extremely
limited
portfolio.
Here,
we
describe
high-throughput
screen
identify
novel
repurposing
snakebite
treatments.
We
present
method
optimisation
384-well
plate,
colorimetric,
screening
assay
allowed
throughput
∼2,800
drugs
per
day,
report
on
∼3,500
post-phase
I
repurposed
library
against
Russell’s
viper,
Daboia
russelii
.
further
explore
broad-spectrum
inhibitory
potential
efficacy
top
hits
range
demonstrate
utility
our
determining
EC
50
s.
Collectively,
findings
support
future
application
this
fully
chemical
space
discover
-inhibiting
value
preventing
severe
pathology
caused
by
envenoming.
BMJ Global Health,
Journal Year:
2024,
Volume and Issue:
9(3), P. e014813 - e014813
Published: March 1, 2024
Antivenom
is
a
lifesaving
medicine
for
treating
snakebite
envenoming,
yet
there
has
been
crisis
in
antivenom
supply
many
decades.
Despite
this,
substantial
quantities
of
stocks
expire
before
use.
This
study
investigated
whether
expired
antivenoms
retain
preclinical
quality
and
efficacy,
with
the
rationale
that
they
could
be
used
emergency
situations
when
in-date
unavailable.
Toxins,
Journal Year:
2025,
Volume and Issue:
17(4), P. 193 - 193
Published: April 11, 2025
Snakebite
envenoming
is
often
discussed
in
terms
of
lethality
and
limb
loss,
but
local
tissue
injury
coagulotoxic
effects
venom
are
significantly
more
common
acute
manifestations
snakebite
(SBE).
Local
the
hemorrhagic
challenging
to
study
live
animals
can
be
ethically
fraught
due
animal
welfare
concerns
such
that
attention
3Rs
motivates
development
vitro
techniques
this
arena.
Herein,
we
tested
use
a
wound-healing
technique
known
as
Electric
Cell-Substrate
Impedance
Sensing
(ECIS)
assess
populations
cultured
cells
exposed
with
or
without
sPLA2
and/or
metalloprotease
inhibitors
(varespladib
marimastat,
respectively).
For
comparison,
StarMax
coagulation
analyzer
for
coagulotoxicity
was
further
used
evaluate
venoms
neutralizing
capabilities
abovementioned
direct
toxin
(DTIs)
against
same
examined
using
ECIS.
Three
viper
three
elapid
were
their
on
H1975
Agkistrodon
contortrix
(Eastern
Copperhead),
Crotalus
helleri
(Southern
Pacific
Rattlesnake),
Vipera
ammodytes
(Horned
Viper)
Naja
atra
(Chinese
Cobra),
mossambica
(Mozambique
Spitting
nigricollis
(Black-necked
respectively.
The
combination
cellular
appears
usefully
discriminate
limitations
specific
inhibit
effects.
This
suggests
ECIS
concomitant
testing
feasible
method
generate
reproducible,
meaningful
preclinical
data
could
any
type
cell
line.
Importantly,
approach
both
quantitative
has
potential
reducing
suffering
during
evaluation
therapeutics.
To
method,
rescue
studies
should
performed.
Expert Opinion on Drug Discovery,
Journal Year:
2025,
Volume and Issue:
unknown, P. 1 - 21
Published: April 29, 2025
Snakebite
envenoming
is
a
neglected
tropical
disease
that
affects
millions
globally
each
year.
In
recent
years,
research
into
the
potential
production
of
recombinant
antivenoms,
formulated
using
mixtures
highly
defined
anti-toxin
monoclonal
antibodies,
has
rapidly
moved
from
theoretical
concept
to
demonstrations
practical
feasibility.
This
article
examines
significant
advancements
in
transitioning
antivenoms
clinical
translation.
The
authors
have
based
their
review
on
literature
obtained
Google
Scholar
and
PubMed
between
September
November
2024.
Coverage
includes
development
validation
antivenom
antibody
discovery
strategies,
characterization
first
broadly
neutralizing
toxin
class
translational
proof-of-concept
experiments.
transition
'concept'
current
situation
where
high-throughput
anti-venom
mAb
becoming
routine,
accompanied
by
increasing
evidence
broad
capacity
vivo,
been
extraordinary.
It
now
important
build
this
momentum
expanding
mAbs
encompass
as
many
classes
possible.
anticipated
key
whether
can
match
or
surpass
existing
conventional
polyvalent
terms
scope
will
be
achieved
next
few
years.
