Current Issues in Molecular Biology,
Journal Year:
2024,
Volume and Issue:
46(8), P. 8852 - 8873
Published: Aug. 14, 2024
Reactive
oxygen
species
(ROS)
are
widely
regarded
as
signaling
molecules
and
play
essential
roles
in
various
cellular
processes,
but
when
present
excess,
they
can
lead
to
oxidative
stress
(OS).
Growing
evidence
suggests
that
the
OS
plays
a
critical
role
pathogenesis
of
HIV
infection
is
associated
with
several
comorbidities
HIV-infected
individuals.
ROS,
generated
both
naturally
during
mitochondrial
metabolism
response
trigger
host
antiviral
responses
also
promote
viral
replication.
While
multifaceted
ROS
pathophysiology
clearly
need
more
investigation,
this
review
paper
unravels
mechanisms
generation
context
infections,
offering
insights
into
protein-mediated
antiretroviral
therapy-generated
OS.
Though
protein
Tat
significantly
attributed
endogenous
increase
post
infection,
sums
up
contribution
other
proteins
HIV-mediated
elicitation
ROS.
Given
investigations
recognizing
significant
onset
progression
diverse
pathologies,
explores
function
mediation
an
array
pathologies
retroviral
therapy.
patients
observed
disruption
antioxidant
defense
system,
therapy
gaining
focus
potential
therapeutic
intervention
well
discussed.
scenario,
further
exploratory
studies
imperative
identifying
alternative
strategies
could
mitigate
toxicities
ART-induced
Nature Communications,
Journal Year:
2019,
Volume and Issue:
10(1)
Published: July 2, 2019
Abstract
Elimination
of
HIV-1
requires
clearance
and
removal
integrated
proviral
DNA
from
infected
cells
tissues.
Here,
sequential
long-acting
slow-effective
release
antiviral
therapy
(LASER
ART)
CRISPR-Cas9
demonstrate
viral
in
latent
infectious
reservoirs
humanized
mice.
subgenomic
fragments,
spanning
the
long
terminal
repeats
Gag
gene,
are
excised
vivo,
resulting
elimination
DNA;
virus
is
not
detected
blood,
lymphoid
tissue,
bone
marrow
brain
by
nested
digital-droplet
PCR
as
well
RNAscope
tests.
No
mediated
off-target
effects
detected.
Adoptive
transfer
human
immunocytes
dual
treated,
virus-free
animals
to
uninfected
mice
fails
produce
progeny
virus.
In
contrast,
readily
following
sole
LASER
ART
or
treatment.
These
data
provide
proof-of-concept
that
permanent
possible.
Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(19)
Published: May 1, 2023
Treatment
of
HIV-1
ADA
-infected
CD34+
NSG-humanized
mice
with
long-acting
ester
prodrugs
cabotegravir,
lamivudine,
and
abacavir
in
combination
native
rilpivirine
was
followed
by
dual
CRISPR-Cas9
C-C
chemokine
receptor
type
five
(CCR5)
proviral
DNA
gene
editing.
This
led
to
sequential
viral
suppression,
restoration
absolute
human
CD4
+
T
cell
numbers,
then
elimination
replication-competent
virus
58%
infected
mice.
Dual
CRISPR
therapies
enabled
the
excision
integrated
cells
contained
within
live
animals.
Highly
sensitive
nucleic
acid
nested
droplet
digital
PCR,
RNAscope,
outgrowth
assays
affirmed
elimination.
not
detected
blood,
spleen,
lung,
kidney,
liver,
gut,
bone
marrow,
brain
virus-free
Progeny
from
adoptively
transferred
CRISPR-treated
neither
nor
recovered.
Residual
fragments
were
easily
seen
untreated
viral-rebounded
No
evidence
off-target
toxicities
recorded
any
treated
Importantly,
therapy
demonstrated
statistically
significant
improvements
cure
percentages
compared
single
treatments.
Taken
together,
these
observations
underscore
a
pivotal
role
combinatorial
editing
achieving
infection.
Chemical Society Reviews,
Journal Year:
2024,
Volume and Issue:
53(4), P. 2099 - 2210
Published: Jan. 1, 2024
Recent
tactical
applications
of
prodrugs
as
effective
tools
in
drug
discovery
and
development
to
resolve
issues
associated
with
delivery
lead
candidates
are
reviewed
a
reflection
the
approval
53
during
2012–2022.
Trends in Neurosciences,
Journal Year:
2020,
Volume and Issue:
43(9), P. 695 - 708
Published: July 15, 2020
HIV
attacks
the
body's
immune
cells,
frequently
compromises
integrity
of
blood-brain
barrier
(BBB),
and
infects
CNS
in
early
stages
infection.
Dysfunction
BBB
further
potentiates
viral
replication
within
CNS,
which
can
lead
to
HIV-associated
neuropathology.
Antiretroviral
therapy
(ART)
significantly
improves
patient
outcomes
reduces
mortality
rates.
However,
there
has
been
limited
progress
targeting
latent
reservoirs
may
eventually
rebound
viremia.
While
ART
drugs
are
shown
be
effective
attenuating
periphery,
protection
brain
by
offers
an
isolated
sanctuary
harbor
maintains
chronic
persistent
CNS.
In
this
review,
we
elucidate
pathology
BBB,
its
ability
potentiate
replication,
as
well
current
therapies
insufficiencies
treating
HIV-infected
individuals.
Advanced Drug Delivery Reviews,
Journal Year:
2018,
Volume and Issue:
148, P. 252 - 289
Published: Oct. 26, 2018
The
discipline
of
neurotheranostics
was
forged
to
improve
diagnostic
and
therapeutic
clinical
outcomes
for
neurological
disorders.
Research
facilitated,
in
largest
measure,
by
the
creation
pharmacologically
effective
multimodal
pharmaceutical
formulations.
Deployment
neurotheranostic
agents
could
revolutionize
staging
nervous
system
disease
outcomes.
However,
obstacles
formulation
design,
drug
loading
payload
delivery
still
remain.
These
will
certainly
be
aided
multidisciplinary
basic
research
teams
with
pharmacology,
nanotechnology,
neuroscience
pharmaceutic
expertise.
When
successful
end
results
provide
"optimal"
platforms.
current
report
reviews
an
extensive
body
knowledge
natural
history,
epidemiology,
pathogenesis
therapeutics
neurologic
eye
on
how,
when
under
what
circumstances
soon
used
as
personalized
medicines
a
broad
range
neurodegenerative,
neuroinflammatory
neuroinfectious
diseases.
