Harnessing Nanohybridized Niclosamide for Precision Mpox Therapeutics
Advanced Healthcare Materials,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 23, 2025
Abstract
Niclosamide,
initially
developed
as
an
anthelmintic,
has
recently
emerged
a
potential
antiviral,
showing
efficacy
against
diverse
viral
threats,
including
Mpox.
As
the
global
health
landscape
faces
recurrent
Mpox
outbreaks,
repurposing
niclosamide
through
advanced
material
strategies
offers
promising
therapeutic
avenues.
This
article
explores
antiviral
mechanisms
of
niclosamide,
focusing
on
how
innovative
nano‐hybrid
formulations
enhance
its
bioavailability
and
pharmacological
performance.
By
leveraging
nanohybridization,
niclosamide's
limitations—such
poor
solubility
bioavailability—are
addressed,
enabling
targeted
delivery
sustained
release.
Early
preclinical
studies
reveal
that
disrupts
replication
entry
processes,
suggesting
utility
option
poxvirus
infections.
Looking
forward,
further
in
vitro,
animal
models,
clinical
investigations
are
essential
to
optimize
application
dosing
for
With
continued
development
materials,
nanohybrid
could
become
critical
tool
managing
related
offering
accessible,
cost‐effective
outbreak
preparedness.
Язык: Английский
Salicylamide derivative JMX0312 protects immunosuppressed Syrian hamsters against adenovirus lethal challenge
Antiviral Research,
Год журнала:
2025,
Номер
unknown, С. 106155 - 106155
Опубликована: Апрель 1, 2025
Язык: Английский
Niclosamide improves cancer immunotherapy by modulating RNA-binding protein HuR-mediated PD-L1 signaling
Cell & Bioscience,
Год журнала:
2023,
Номер
13(1)
Опубликована: Окт. 17, 2023
Immune
checkpoint
blockade
(ICB)
represents
a
revolutionary
advance
in
cancer
treatment
but
remains
limited
success
triple-negative
breast
(TNBC).
Here
we
aim
to
explore
the
mechanism
of
RNA-binding
protein
(RBP)
HuR
immune
evasion
by
post-transcriptionally
regulating
PD-L1
and
evaluate
potential
inhibition
improve
response.The
binding
between
mRNA
was
determined
ribonucleoprotein
immunoprecipitation
RNA
pull-down
assays.
The
knockout
clones
were
established
CRISPR/Cas9
technology.
levels
assessed
Western
blot,
immunohistochemistry,
immunocytochemistry.
function
molecular
HuR-PD-L1
vitro
T
cell
activation
killing
assay
vivo
efficacy
assay.We
found
that
directly
bound
stabilized
mRNA.
Knocking
out
reduced
promoted
activation.
We
discovered
niclosamide
inhibiting
cytoplasmic
translocation,
diminished
glycosylation
PD-L1.
Niclosamide
enhanced
cell-mediated
cells
significantly
improved
anti-PD-1
immunotherapy
two
syngeneic
animal
tumor
models.We
identified
as
novel
posttranscriptional
regulator
PD-L1,
which
plays
an
important
role
evasion.
might
be
promising
repurposed
drug
patient
response
targeting
axis.
Our
study
demonstrates
strategy
for
HuR/PD-L1
provides
first
proof-of-principle
repurposing
inhibitor
overcome
ICB
immunotherapy.
Язык: Английский
Repurposing Niclosamide to Modulate Renal RNA-Binding Protein HuR for the Treatment of Diabetic Nephropathy in db/db Mice
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9651 - 9651
Опубликована: Сен. 6, 2024
Hu
antigen
R
(HuR)
plays
a
key
role
in
regulating
genes
critical
to
the
pathogenesis
of
diabetic
nephropathy
(DN).
This
study
investigates
therapeutic
potential
niclosamide
(NCS)
as
an
HuR
inhibitor
DN.
Uninephrectomized
mice
were
assigned
four
groups:
normal
control;
untreated
db/db
terminated
at
14
and
22
weeks,
respectively;
treated
with
NCS
(20
mg/kg
daily
via
i.p.)
from
weeks
18
22.
Increased
expression
was
observed
kidneys
mice,
which
mitigated
by
treatment.
Untreated
exhibited
obesity,
progressive
hyperglycemia,
albuminuria,
kidney
hypertrophy
glomerular
mesangial
matrix
expansion,
increased
renal
production
fibronectin
a-smooth
muscle
actin,
decreased
WT-1+-podocytes
nephrin
expression.
treatment
did
not
affect
mouse
body
weight,
but
reduced
blood
glucose
HbA1c
levels
halted
DN
progression
mice.
Renal
inflammatory
oxidative
stress
markers
(NF-κBp65,
TNF-a,
MCP-1)
urine
MDA
during
disease
Additionally,
Wnt1-signaling-pathway
downstream
factor,
Wisp1,
identified
mediator
HuR-dependent
action
found
be
markedly
kidneys,
normalized
These
findings
suggest
that
inhibition
is
for
improving
inflammation,
stress.
The
reduction
Wisp1
also
contributes
its
renoprotective
effects.
supports
repurposing
inhibitors
novel
therapy
Язык: Английский
Drug Repurposing: Research Progress of Niclosamide and Its Derivatives on Antibacterial Activity
Infection and Drug Resistance,
Год журнала:
2024,
Номер
Volume 17, С. 4539 - 4556
Опубликована: Окт. 1, 2024
The
development
of
antibiotic
resistance
complicates
the
treatment
infectious
diseases
and
is
a
global
public
health
threat.
However,
drug
repurposing
can
address
this
issue
reduce
research
costs.
Niclosamide
salicylanilide
compound
approved
by
Food
Drug
Administration
(FDA),
it
has
been
used
clinically
for
treating
parasitic
infections
many
years.
Recent
studies
have
shown
that
niclosamide
inhibit
bacterial
fungus
activity
affecting
quorum
sensing
system,
biofilm
formation,
cell
membrane
potential,
other
mechanisms.
Here,
we
discuss
recent
advances
in
antimicrobial
applications
its
derivatives
to
provide
new
perspectives
diseases.
Язык: Английский
In Vitro Screening of an In-House Library of Structurally Distinct Chemotypes Towards the Identification of Novel SARS-CoV-2 Inhibitors
Pharmaceuticals,
Год журнала:
2024,
Номер
17(12), С. 1668 - 1668
Опубликована: Дек. 11, 2024
Background/Objectives:
Four
years
after
the
COVID-19
pandemic,
a
very
limited
number
of
drugs
has
been
marketed;
thus,
search
for
new
medications
still
represents
compelling
need.
In
our
previous
work
on
antiviral,
antiparasitic,
and
antiproliferative
agents,
we
described
several
compounds
(1–13
16–20)
structurally
related
to
clofazimine,
chloroquine,
benzimidazole
derivatives.
Thus,
deemed
it
worthwhile
test
them
against
replication
SARS-CoV-2,
together
with
few
other
(14,
15
21–25),
which
showed
some
analogy
miscellaneous
anti-coronavirus
agents.
Methods:
Twenty-five
assorted
were
evaluated
in
vitro
cytotoxicity
Vero
E6
their
ability
inhibit
SARS-CoV-2
replication.
Results:
Several
(2,
3,
10,
11,
13–15,
18–20)
demonstrated
antiviral
activity
(IC50
range
1.5–28
µM)
six
exhibited
an
interesting
selectivity
index
4.5–20.
The
chloroquine
analogs
10
11
more
potent
than
reference
itself
doubled
its
SI
value
(20
versus
11).
Also,
ring
emerged
as
valuable
scaffold,
originating
(13–15
endowed
anti-SARS-CoV-2
activity.
Despite
modest
activity,
cytisine
arylamino
enone
derivatives
23
25,
respectively,
also
deserve
further
consideration
model
compounds.
Conclusions:
investigated
chemotypes
may
represent
hit
compounds,
deserving
in-depth
biological
studies
define
mechanisms
action.
derived
information
will
guide
subsequent
chemical
optimization
towards
development
efficient
Язык: Английский