International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 2912 - 2912
Опубликована: Март 23, 2025
Influenza
viruses
are
characterized
by
their
high
variability
and
pathogenicity,
effective
therapeutic
options
remain
limited.
Given
these
challenges,
targeting
host
cell
proteins
that
facilitate
viral
replication
presents
a
promising
strategy
for
antiviral
drug
discovery.
In
the
present
study,
we
observed
significant
upregulation
of
Glycyl-tRNA
synthetase
(GlyRS)
within
24
h
post-PR8
virus
infection.
The
inhibition
GlyRS
expression
in
A549
cells
resulted
marked
reduction
infection
rates
across
multiple
influenza
strains,
while
overexpression
led
to
an
increase
infectivity
during
early
stages
These
findings
suggest
plays
critical
role
virus.
Accordingly,
screened
potential
inhibitors
identified
Lycobetaine
Scutellarein
using
multifaceted
approach.
Through
combination
molecular
dynamics
simulations,
further
elucidated
mechanisms
action
binding
sites
compounds.
Both
effectively
suppressed
viruses,
activity
was
confirmed
be
mediated
targeting.
Therefore,
inhibitors,
such
as
Scutellarein,
represent
candidates
combating
infections
provide
novel
insights
into
treatment
aaRS-related
diseases,
opening
new
avenues
development
aaRS-targeted
therapeutics.
Frontiers in Molecular Biosciences,
Год журнала:
2023,
Номер
10
Опубликована: Май 18, 2023
Infectious
diseases
continue
to
be
a
major
cause
of
morbidity
and
mortality
worldwide.
Diseases
perturbation
the
host's
immune
system
provoking
response
that
involves
genes,
proteins
metabolites.
While
genes
are
regulated
by
epigenetic
or
other
host
factors,
can
undergo
post-translational
modification
enable/modify
function.
As
result,
it
is
difficult
correlate
disease
phenotype
based
solely
on
genetic
proteomic
information
only.
Metabolites,
however,
provide
direct
biochemical
activity
during
diseased
state.
Therefore,
metabolites
may,
potentially,
represent
phenotypic
signature
Measuring
assessing
in
large
scale
falls
under
omics
technology
known
as
"metabolomics".
Comprehensive
and/or
specific
metabolic
profiling
biological
fluids
used
biomarkers
diagnosis.
In
addition,
metabolomics
together
with
genomics
differentiate
patients
differential
treatment
development
targeted
therapy
instead
pathogen
where
pathogens
more
prone
mutation
lead
antimicrobial
resistance.
Thus,
for
patient
stratification,
personalized
drug
formulation
control
management.
Currently,
several
therapeutics
vitro
diagnostics
kits
have
been
approved
US
Food
Drug
Administration
(FDA)
diagnosis
infectious
diseases.
However,
actual
number
required
tailored
limited
medicine
require
involvement
personnel
from
multidisciplinary
fields
ranging
technological
development,
bioscience,
bioinformatics,
biostatistics,
clinicians,
biotechnology
companies.
Given
significance
metabolomics,
this
review,
we
discussed
different
aspects
particularly
potentials
diagnostic
use
small
molecules
diseases,
their
scopes
challenges
medicine.
Molecules,
Год журнала:
2023,
Номер
28(4), С. 1981 - 1981
Опубликована: Фев. 20, 2023
Respiratory
viruses
represent
a
world
public
health
problem,
giving
rise
to
annual
seasonal
epidemics
and
several
pandemics
caused
by
some
of
these
viruses,
including
the
COVID-19
pandemic
novel
SARS-CoV-2,
which
continues
date.
Some
antiviral
drugs
have
been
licensed
for
treatment
influenza,
but
they
cause
side
effects
lead
resistant
viral
strains.
Likewise,
aerosolized
ribavirin
is
only
drug
approved
therapy
infections
respiratory
syncytial
virus,
it
possesses
various
limitations.
On
other
hand,
no
specific
are
treat
diseases.
In
this
sense,
natural
products
their
derivatives
appeared
as
promising
alternatives
in
searching
new
compounds
with
activity.
Besides
chemical
properties,
quinones
demonstrated
interesting
biological
activities,
activity
against
viruses.
This
review
summarizes
molecular
targets
different
types
(both
synthetic).
Thus,
present
work
offers
general
overview
importance
an
option
future
pharmacological
infections,
subject
additional
studies
that
support
effectiveness
safety.
Arboviruses
have
the
potential
to
spread
quickly
and
cause
a
global
health
emergency.
These
are
RNA
viruses
that
use
RNA-dependent
polymerase
(RdRp)
for
their
replication.
RdRp
lacks
proofreading
activity,
leading
high
error
rates,
low
replicative
fidelity,
more
genetic
variability.
In
addition,
shorter
generation
time
faster
evolutionary
rate
of
these
lead
re-emergence
recurrence
arboviral
infections
due
emergence
new
variants
development
antiviral
resistance.
During
replication
inside
host
cell
through
protein-protein
interactions
(PPIs),
interact
with
several
factors
utilize
cellular
machinery
benefit.
Besides
this,
employ
transmission
strategies
combat
innate
adaptive
immune
responses
by
manipulating
signaling
metabolic
pathways
hosts.
Hence,
therapies
targeting
host-virus
PPIs
can
provide
an
alternative
broad-spectrum
strategy
against
viruses.
The
approach
virus-specific
proteins
developing
antivirals
is
expected
solve
problem
drug
resistance
emerging
This
review
focuses
on
directly
affect
pathways.
Better
understanding
mechanisms
will
develop
therapeutic
tools
treat
viral
infections.
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 24, 2024
Abstract
Protein
Phosphatase
1
(PP1)
is
a
major
serine/threonine
phosphatase
in
eukaryotes,
participating
several
cellular
processes
and
metabolic
pathways.
Due
to
their
low
substrate
specificity,
PP1’s
catalytic
subunits
do
not
exist
as
free
entities
but
instead
bind
Regulatory
Interactors
of
One
(RIPPO),
which
regulate
specificity
subcellular
localization.
Most
RIPPOs
PP1
through
combinations
short
linear
motifs
(4–12
residues),
forming
highly
specific
holoenzymes.
These
PP1-binding
may,
hence,
represent
attractive
targets
for
the
development
drugs
that
interfere
with
subset
Several
viruses
exploit
host
cell
protein
(de)phosphorylation
machinery
ensure
efficient
virus
particle
formation
propagation.
While
role
many
kinases
viral
life
cycles
has
been
extensively
studied,
targeting
phosphatases
by
proteins
studied
less
detail.
Here,
we
compile
review
what
known
concerning
context
infections
discuss
how
it
may
constitute
putative
host-based
target
novel
antiviral
strategies.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2024,
Номер
unknown, С. 1 - 20
Опубликована: Март 7, 2024
The
significant
mortality
rate
associated
with
Marburg
virus
infection
made
it
the
greatest
hazard
among
infectious
diseases.
Drug
repurposing
using
in
silico
methods
has
been
crucial
identifying
potential
compounds
that
could
prevent
viral
replication
by
targeting
virus's
primary
proteins.
This
study
aimed
at
drugs
of
SARS-CoV-2
for
candidates
against
matrix
protein
VP40
virus.
Virtual
screening
was
performed
where
control
compound,
Nilotinib,
showed
a
binding
score
−9.99
kcal/mol.
Based
on
scores,
hit
9549298,
11960895,
44545852,
51039094,
and
89670174
were
selected
had
lower
than
control.
Subsequent
molecular
dynamics
(MD)
simulation
revealed
compound
9549298
consistently
formed
hydrogen
bond
residue
Gln290.
observed
both
docking
MD
poses,
indicating
strong
interaction
protein.
11960895
most
stable
consistent
RMSD
pattern
exhibited
100
ns
simulation,
while
identical
plot
compared
to
molecule.
MM/PBSA
analysis
free
energy
(ΔG)
control,
−30.84
−38.86
kcal/mol,
respectively.
It
PCA
(principal
component
analysis)
FEL
(free
landscape)
lesser
conformational
variation.
Overall,
this
proposed
as
binders
MARV
can
cause
its
inhibition,
however
inherently
lacks
experimental
validation.
Furthermore,
proposes
in-vitro
experiments
next
step
validate
these
computational
findings,
offering
practical
approach
further
explore
compounds'
antiviral
agents.
PubMed,
Год журнала:
2024,
Номер
49(3), С. 312 - 318
Опубликована: Фев. 5, 2024
This
observational
study
included
all
patients
undergoing
HCV
treatment
with
direct-acting
antiviral
(DAA)-based
therapy
between
May
2020
and
September
2023
at
the
Dolj
County
Hospital,
Romania.
The
aim
was
to
investigate
adherence
DAAs
among
effect
of
this
on
their
health-related
quality
life
(HRQoL).
Chronic
HCV-infected
were
prospectively
evaluated
baseline
(T0),
before
beginning
treatment,
12
weeks
after
completing
(T1).
HCV-AD10
questionnaire
used
measure
adherence,
HRQoL
assessed
15D
instrument.
administered
two
time
points:
T0
T1,
during
which
Sustained
Virologic
Response
(SVR)
also
measured.
primary
outcome
secondary
outcomes
including
(QoL),
sustained
virologic
response
(SVR).
based
initiated
for
368
patients,
whom
health
insured.
psychological
state
clinically
improved.
very
good
(mean±SD,
91.51±8.34),
being
influenced
by
age
(younger
much
adherent,
rho=-0.112,
p-value=0.031)
severity
disease
(patients
more
severe
hepatitis
less
rho=-0.167,
p-value=0.001).
had
a
significant
improving
but
did
not
influence
medication
adherence.
Viruses,
Год журнала:
2023,
Номер
15(2), С. 568 - 568
Опубликована: Фев. 19, 2023
Despite
the
great
technological
and
medical
advances
in
fighting
viral
diseases,
new
therapies
for
most
of
them
are
still
lacking,
existing
antivirals
suffer
from
major
limitations
regarding
drug
resistance
a
limited
spectrum
activity.
In
fact,
approved
directly
acting
antiviral
(DAA)
drugs,
which
interfere
with
proteins
confer
selectivity
towards
their
targets
but
spectrum.
Nowadays,
host-targeted
(HTAs)
on
rise,
discovery
development
pipelines,
academia
pharmaceutical
industry.
These
drugs
target
host
involved
virus
life
cycle
considered
promising
alternatives
to
DAAs
due
broader
lower
potential
resistance.
Herein,
we
discuss
an
important
class
HTAs
that
modulate
signal
transduction
pathways
by
targeting
kinases.
Kinases
key
enzymes
control
virus-host
interactions.
We
also
provide
synopsis
pipeline
detailing
kinase
targets,
types,
therapeutic
classes
repurposed
top
developing
organizations.
Furthermore,
detail
design
repurposing
considerations,
as
well
challenges,
kinase-targeted
antivirals,
including
choice
binding
sites,
physicochemical
properties,
combinations.
Journal of Translational Medicine,
Год журнала:
2024,
Номер
22(1)
Опубликована: Янв. 2, 2024
Abstract
Liver
cancer
is
a
major
malignant
tumor,
which
seriously
threatens
human
health
and
increases
the
economic
burden
on
patients.
At
present,
gene
therapy
has
been
comprehensively
studied
as
an
excellent
therapeutic
measure
in
liver
treatment.
Oncolytic
virus
(OV)
kind
of
that
can
specifically
infect
kill
tumor
cells.
After
being
modified
by
genetic
engineering,
specificity
OV
infection
to
cells
increased,
its
influence
normal
reduced.
To
date,
shown
effectiveness
safety
experimental
clinical
studies
variety
tumors.
Thus,
this
review
primarily
introduces
current
status
different
genetically
engineered
OVs
used
for
cancer,
focuses
application
target
genes
therapy,
identifies
problems
encountered
OVs-based
combination
corresponding
solutions,
will
provide
new
insights
into
treatment
cancer.
