Angiotensin-converting
enzyme
2
(ACE2)
is
a
major
cell
entry
receptor
for
severe
acute
respiratory
syndrome
coronavirus
(SARS-CoV-2).
The
induction
of
ACE2
expression
may
serve
as
strategy
by
SARS-CoV-2
to
facilitate
its
propagation.
However,
the
regulatory
mechanisms
after
viral
infection
remain
largely
unknown.
Using
45
different
luciferase
reporters,
transcription
factors
SP1
and
HNF4α
were
found
positively
negatively
regulate
expression,
respectively,
at
transcriptional
level
in
human
lung
epithelial
cells
(HPAEpiCs).
increased
activity
while
inhibiting
that
HNF4α.
PI3K/AKT
signaling
pathway,
activated
infection,
served
crucial
node,
inducing
enhancing
phosphorylation—a
marker
activity—and
reducing
nuclear
localization
colchicine
treatment
inhibited
thereby
suppressing
expression.
In
Syrian
hamsters
(
Mesocricetus
auratus
)
infected
with
SARS-CoV-2,
inhibition
either
mithramycin
A
or
resulted
reduced
replication
tissue
injury.
summary,
our
study
uncovers
novel
function
regulation
identifies
potential
target
reduce
infection.
Nature Reviews Molecular Cell Biology,
Journal Year:
2022,
Volume and Issue:
23(6), P. 407 - 427
Published: Feb. 28, 2022
Human
topoisomerases
comprise
a
family
of
six
enzymes:
two
type
IB
(TOP1
and
mitochondrial
TOP1
(TOP1MT),
IIA
(TOP2A
TOP2B)
IA
(TOP3A
TOP3B)
topoisomerases.
In
this
Review,
we
discuss
their
biochemistry
roles
in
transcription,
DNA
replication
chromatin
remodelling,
highlight
the
recent
progress
made
understanding
TOP3A
TOP3B.
Because
advances
elucidating
high-order
organization
genome
through
loops
topologically
associating
domains
(TADs),
integrate
functions
with
organization.
We
also
physiological
pathological
formation
irreversible
topoisomerase
cleavage
complexes
(TOPccs)
as
they
generate
DNA–protein
crosslinks
(TOP-DPCs)
coupled
breaks.
expanding
number
redundant
pathways
that
repair
TOP-DPCs,
defects
those
pathways,
which
are
increasingly
recognized
source
genomic
damage
leading
to
neurological
diseases
cancer.
Topoisomerases
have
essential
replication,
remodelling
and,
recently
revealed,
3D
However,
breaks,
disease-causing
damage.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: April 29, 2022
The
global
coronavirus
disease
2019
(COVID-19)
pandemic
is
currently
ongoing.
It
caused
by
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
A
high
proportion
of
COVID-19
patients
exhibit
gastrointestinal
manifestations
such
as
diarrhea,
nausea,
or
vomiting.
Moreover,
the
and
tracts
are
primary
habitats
human
microbiota
targets
for
SARS-CoV-2
infection
they
express
angiotensin-converting
enzyme-2
(ACE2)
transmembrane
protease
serine
(TMPRSS2)
at
levels.
There
accumulating
evidence
that
significantly
altered
in
with
post-acute
(PACS).
Microbiota
powerful
immunomodulatory
factors
various
diseases,
diabetes,
obesity,
cancers,
ulcerative
colitis,
Crohn's
disease,
certain
viral
infections.
In
present
review,
we
explore
associations
between
host
terms
their
clinical
relevance.
Microbiota-derived
metabolites
components
main
mediators
microbiota-host
interactions
influence
immunity.
Hence,
discuss
potential
mechanisms
which
microbiota-derived
modulate
immune
responses
to
infection.
Finally,
review
a
variety
possible
microbiota-based
prophylaxes
therapies
PACS,
including
fecal
transplantation
(FMT),
probiotics,
prebiotics,
metabolites,
engineered
symbiotic
bacteria.
This
treatment
strategy
could
mitigate
virus-induced
inflammation.
Cell Reports Medicine,
Journal Year:
2021,
Volume and Issue:
2(8), P. 100369 - 100369
Published: July 21, 2021
There
is
an
urgent
need
to
identify
which
COVID-19
patients
will
develop
life-threatening
illness
so
that
medical
resources
can
be
optimally
allocated
and
rapid
treatment
administered
early
in
the
disease
course,
when
clinical
management
most
effective.
To
aid
prognostic
classification
of
severity,
we
perform
untargeted
metabolomics
on
plasma
from
339
patients,
with
samples
collected
at
six
longitudinal
time
points.
Using
temporal
metabolic
profiles
machine
learning,
build
a
predictive
model
severity.
We
discover
panel
metabolites
measured
study
entry
successfully
determines
Through
analysis
samples,
confirm
these
markers
are
directly
related
progression
their
levels
return
baseline
upon
recovery.
Finally,
validate
also
altered
hamster
COVID-19.
Nature Metabolism,
Journal Year:
2021,
Volume and Issue:
3(11), P. 1466 - 1475
Published: Sept. 27, 2021
Caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
COVID-19
is
a
virus-induced
inflammatory
disease
of
the
airways
and
lungs
that
leads
to
multi-organ
damage
death.
Here
we
show
cellular
lipid
synthesis
required
for
SARS-CoV-2
replication
offers
an
opportunity
pharmacological
intervention.
Screening
short-hairpin
RNA
sublibrary
targets
metabolic
genes,
identified
genes
either
inhibit
or
promote
viral
infection,
including
two
key
candidate
ACACA
FASN,
which
operate
in
same
pathway.
We
further
screened
several
potent
inhibitors
fatty
acid
synthase
(encoded
FASN),
US
Food
Drug
Administration-approved
anti-obesity
drug
orlistat,
found
it
inhibits
vitro
variants,
more
contagious
new
such
as
Delta.
In
mouse
model
infection
(K18-hACE2
transgenic
mice),
injections
orlistat
resulted
lower
levels
lung,
reduced
lung
pathology
increased
survival.
Our
findings
identify
candidates
prevention
treatment
inhibiting
replication.
Clinical
trials
are
needed
evaluate
efficacy
repurposing
humans.
Pharmacological
synthase,
approved
shown
vivo.
