iScience,
Год журнала:
2022,
Номер
25(11), С. 105319 - 105319
Опубликована: Окт. 10, 2022
SARS-CoV-2
infection
induces
imbalanced
immune
response
such
as
hyperinflammation
in
patients
with
severe
COVID-19.
Here,
we
studied
the
immunometabolic
regulatory
mechanisms
for
pathogenesis
of
We
depicted
metabolic
landscape
cells,
especially
macrophages,
from
bronchoalveolar
lavage
fluid
COVID-19
at
single-cell
level.
found
that
most
processes
were
upregulated
macrophages
lungs
mild
compared
to
cells
healthy
controls,
whereas
showed
downregulation
core
pathways
including
glutamate
metabolism,
fatty
acid
oxidation,
citrate
cycle,
and
oxidative
phosphorylation,
upregulation
a
few
glycolysis.
Rewiring
cellular
metabolism
by
amino
supplementation,
glycolysis
inhibition,
or
PPARγ
stimulation
reduces
inflammation
stimulated
SARS-CoV-2.
Altogether,
this
study
demonstrates
imbalance
may
contribute
provides
insights
into
treating
modulation.
BMC Infectious Diseases,
Год журнала:
2022,
Номер
22(1)
Опубликована: Авг. 4, 2022
At
present,
no
single
efficacious
therapeutic
exists
for
acute
COVID-19
management
and
a
multimodal
approach
may
be
necessary.
2-deoxy-D-glucose
(2-DG)
is
metabolic
inhibitor
that
has
been
shown
to
limit
multiplication
of
SARS-CoV-2
in-vitro.
We
evaluated
the
efficacy
safety
2-DG
as
adjunct
standard
care
in
treatment
moderate
severe
patients.We
conducted
randomized,
open-label,
phase
II,
clinical
study
evaluate
efficacy,
safety,
tolerability
administered
(SOC).
A
total
110
patients
between
ages
18
65
years
with
were
included.
Patients
randomized
receive
63,
90,
or
126
mg/kg/day
addition
SOC
only.
Times
maintaining
SpO2
≥
94%
on
room
air,
discharge,
recovery,
vital
signs
normalisation,
improvement
by
1
2
points
WHO
progression
scale,
negative
conversion
RT-PCR,
requirement
intensive
care,
mortality
analyzed
assess
efficacy.Patients
treated
90
plus
showed
better
outcomes.
Time
was
significantly
shorter
mg
compared
(median
2.5
days
vs.
5
days,
Hazard
ratio
[95%
confidence
interval]
=
2.3
[1.14,
4.64],
p
0.0201).
discharge
from
isolation
ward,
normalization
group.
All
three
doses
well
tolerated.
Thirty-three
(30.3%)
reported
adverse
events
mostly
(86%)
mild.2-DG
benefit
over
alone
COVID-19.
The
promising
trends
observed
current
II
encouraging
confirmatory
evaluation
larger
III
trial.CTRI,
CTRI/2020/06/025664.
Registered
5th
June
2020,
http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27
.
Communications Biology,
Год журнала:
2022,
Номер
5(1)
Опубликована: Сен. 30, 2022
Abstract
SARS-CoV-2
infection
causes
COVID-19,
a
severe
acute
respiratory
disease
associated
with
cardiovascular
complications
including
long-term
outcomes.
The
presence
of
virus
in
cardiac
tissue
patients
COVID-19
suggests
this
is
direct,
rather
than
secondary,
effect
infection.
Here,
by
expressing
individual
proteins
the
Drosophila
heart,
we
demonstrate
interaction
Nsp6
host
MGA/MAX
complex
(MGA,
PCGF6
and
TFDP1).
Complementing
transcriptomic
data
from
fly
heart
reveal
that
blocks
antagonistic
complex,
which
shifts
balance
towards
MYC/MAX
activates
glycolysis—with
similar
findings
mouse
cardiomyocytes.
Further,
-induced
glycolysis
disrupts
mitochondrial
function,
known
to
increase
reactive
oxygen
species
(ROS)
failure;
could
explain
COVID-19-associated
pathology.
Inhibiting
pathway
2-deoxy-D-glucose
(2DG)
treatment
attenuates
phenotype
flies
mice.
These
point
as
potential
pharmacological
target
for
treating
failure.
Molecules,
Год журнала:
2022,
Номер
27(18), С. 5928 - 5928
Опубликована: Сен. 12, 2022
Viral
infection
almost
invariably
causes
metabolic
changes
in
the
infected
cell
and
several
types
of
host
cells
that
respond
to
infection.
Among
changes,
most
prominent
is
upregulated
glycolysis
process
as
main
pathway
glucose
utilization.
Glycolysis
activation
a
common
mechanism
adaptation
viral
infections,
including
noroviruses,
rhinoviruses,
influenza
virus,
Zika
cytomegalovirus,
coronaviruses
others.
Such
provide
potential
targets
for
therapeutic
approaches
could
reduce
impact
inhibitors,
especially
2-deoxy-D-glucose
(2-DG),
have
been
intensively
studied
antiviral
agents.
However,
2-DG’s
poor
pharmacokinetic
properties
limit
its
wide
clinical
application.
Herein,
we
discuss
2-DG
novel
analogs
potent
promising
drugs
with
special
emphasis
on
targeted
intracellular
processes.
Molecules,
Год журнала:
2023,
Номер
28(5), С. 2332 - 2332
Опубликована: Март 2, 2023
The
COVID-19
pandemic
has
flared
across
every
part
of
the
globe
and
affected
populations
from
different
age
groups
differently.
People
aged
40
to
80
years
or
older
are
at
an
increased
risk
morbidity
mortality
due
COVID-19.
Therefore,
there
is
urgent
requirement
develop
therapeutics
decrease
disease
in
population.
Over
last
few
years,
several
prodrugs
have
demonstrated
significant
anti-SARS-CoV-2
effects
vitro
assays,
animal
models,
medical
practice.
Prodrugs
used
enhance
drug
delivery
by
improving
pharmacokinetic
parameters,
decreasing
toxicity,
attaining
site
specificity.
This
article
discusses
recently
explored
such
as
remdesivir,
molnupiravir,
favipiravir,
2-deoxy-D-glucose
(2-DG)
their
implications
population,
well
investigating
recent
clinical
trials.
ACS Applied Materials & Interfaces,
Год журнала:
2024,
Номер
16(8), С. 10565 - 10579
Опубликована: Фев. 20, 2024
Post-traumatic
hemorrhage,
which
can
result
from
accidents
or
battlefield
injuries,
is
a
significant
global
concern
due
to
the
high
prehospital
mortality
rate.
Substantial
efforts
have
been
made
develop
hemostatic
agents
that
effectively
reduce
hemorrhage
in
immediate
aftermath
of
traumatic
event.
The
present
study
investigated
potential
efficacy
Ca2+
and
Zn2+
supplemented
sodium
alginate-based
dry
particles
(SA-CZ
DHP)
manage
excessive
blood
loss
post-traumatic
hemorrhage.
SA-CZ
DHP
were
developed,
followed
by
their
physical
biochemical
characterization,
cytocompatibility
hemocompatibility
testing,
critical
evaluation
vitro
vivo.
safe
showed
absorption
accelerated
clotting
kinetics
with
reduced
coagulation
time
(≈70%,
p
<
0.0001)
whole
human
blood,
observed
insignificant
hemolysis
uninterrupted
RBC
morphology.
significantly
mean
(≈90%
SD
rats
tail
incision),
bleeding
(≈60%
BALB/c
mice
incision)
was
at
par
commercially
available
Celox
granules.
In
conclusion,
biocompatible
exhibited
rapid
effective
management
loss.
It
also
pertinent
note
developed
formulation
could
be
cost-effective
alternative
its
commercial
counterparts.
Viruses,
Год журнала:
2023,
Номер
15(5), С. 1040 - 1040
Опубликована: Апрель 23, 2023
Severe
Acute
Respiratory
Syndrome
Coronavirus-2
(SARS-CoV-2)
canonically
utilizes
clathrin-mediated
endocytosis
(CME)
and
several
other
endocytic
mechanisms
to
invade
airway
epithelial
cells.
Endocytic
inhibitors,
particularly
those
targeting
CME-related
proteins,
have
been
identified
as
promising
antiviral
drugs.
Currently,
these
inhibitors
are
ambiguously
classified
chemical,
pharmaceutical,
or
natural
inhibitors.
However,
their
varying
may
suggest
a
more
realistic
classification
system.
Herein,
we
present
new
mechanistic-based
of
in
which
they
segregated
among
four
distinct
classes
including:
(i)
that
disrupt
endocytosis-related
protein-protein
interactions,
assembly
dissociation
complexes;
(ii)
large
dynamin
GTPase
and/or
kinase/phosphatase
activities
associated
with
endocytosis;
(iii)
modulate
the
structure
subcellular
components,
especially
plasma
membrane,
actin;
(iv)
cause
physiological
metabolic
alterations
niche.
Excluding
drugs
designed
halt
SARS-CoV-2
replication,
drugs,
either
FDA-approved
suggested
through
basic
research,
could
be
systematically
assigned
one
classes.
We
observed
many
anti-SARS-CoV-2
included
class
III
IV
interfere
structural
integrity
respectively.
This
perspective
contribute
our
understanding
relative
efficacy
support
optimization
individual
combined
potential
against
SARS-CoV-2.
selectivity,
effects,
possible
interactions
non-endocytic
cellular
targets
need
clarification.
Communications Biology,
Год журнала:
2023,
Номер
6(1)
Опубликована: Апрель 7, 2023
Abstract
Cellular
metabolic
dysregulation
is
a
consequence
of
SARS-CoV-2
infection
that
key
determinant
disease
severity.
However,
how
perturbations
influence
immunological
function
during
COVID-19
remains
unclear.
Here,
using
combination
high-dimensional
flow
cytometry,
cutting-edge
single-cell
metabolomics,
and
re-analysis
transcriptomic
data,
we
demonstrate
global
hypoxia-linked
switch
from
fatty
acid
oxidation
mitochondrial
respiration
towards
anaerobic,
glucose-dependent
metabolism
in
CD8
+
Tc,
NKT,
epithelial
cells.
Consequently,
found
strong
immunometabolism
was
tied
to
increased
cellular
exhaustion,
attenuated
effector
function,
impaired
memory
differentiation.
Pharmacological
inhibition
mitophagy
with
mdivi-1
reduced
excess
glucose
metabolism,
resulting
enhanced
generation
SARS-CoV-2-
specific
cytokine
secretion,
augmented
cell
proliferation.
Taken
together,
our
study
provides
critical
insight
regarding
the
mechanisms
underlying
effect
on
host
immune
highlights
as
promising
therapeutic
target
for
treatment.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115637 - 115637
Опубликована: Окт. 14, 2023
COVID-19,
caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
emerged
as
a
global
health
threat
in
2019.
An
important
feature
of
the
disease
is
that
multiorgan
symptoms
SARS-CoV-2
infection
persist
after
recovery.
Evidence
indicates
people
who
recovered
from
even
those
under
age
65
years
without
cardiovascular
risk
factors
such
smoking,
obesity,
hypertension,
and
diabetes,
had
significantly
increased
for
up
to
one
year
diagnosis.
Therefore,
it
closely
monitor
individuals
have
COVID-19
potential
damage
may
manifest
at
later
stage.
Ferroptosis
an
iron-dependent
form
non-apoptotic
cell
death
characterized
production
reactive
oxygen
species
(ROS)
lipid
peroxide
levels.
Several
studies
demonstrated
ferroptosis
plays
role
cancer,
ischemia/reperfusion
injury
(I/RI),
other
diseases.
Altered
iron
metabolism,
upregulation
species,
glutathione
peroxidase
4
inactivation
are
striking
features
COVID-19-related
injury.
can
cause
ferroptosis,
leading
damage.
Understanding
mechanism
injuries
will
contribute
development
treatment
regimens
preventing
or
reducing
complications.
In
this
article,
we
go
over
pathophysiological
underpinnings
SARS-CoV-2-induced
chronic
injury,
function
prospective
approaches.