International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(11), С. 6123 - 6123
Опубликована: Май 30, 2022
The
SARS-CoV-2
pandemic
has
created
a
global
public
crisis
and
heavily
affected
personal
lives,
healthcare
systems,
economies.
Virus
variants
are
continuously
emerging,
and,
thus,
the
been
ongoing
for
over
two
years.
Vaccines
were
rapidly
developed
based
on
original
(Wuhan-Hu-1)
to
build
immunity
against
coronavirus
disease.
However,
they
had
very
low
effect
virus’
due
their
cross-reactivity.
In
this
study,
multivalent
vaccine
was
using
ferritin
nanocages,
which
display
spike
protein
from
Wuhan-Hu-1,
B.1.351,
or
B.1.429
surfaces.
We
show
that
mixture
of
three
spike-protein-displaying
nanocages
elicits
CD4+
CD8+
T
cells
B-cell
successfully
in
vivo.
Furthermore,
generate
more
consistent
antibody
response
B.1.351
than
monovalent
vaccine.
This
leads
us
believe
proposed
ferritin-nanocage-based
platform
will
provide
strong
protection
emerging
concern
(VOCs).
Journal of Medical Virology,
Год журнала:
2021,
Номер
94(1), С. 63 - 81
Опубликована: Сен. 1, 2021
Although
significant
research
has
been
done
to
find
effective
drugs
against
coronavirus
disease
2019
(COVID-19)
caused
by
severe
acute
respiratory
syndrome
2
(SARS-CoV-2),
no
definite
drug
exists.
Thus,
now
shifted
towards
immunomodulatory
agents
other
than
antivirals.
In
this
review,
we
aim
describe
the
latest
findings
on
role
of
type
I
interferon
(IFN)-mediated
innate
antiviral
response
SARS-CoV-2
and
discuss
use
IFNs
as
a
medication
for
COVID-19.
A
growing
body
evidence
indicated
promoting
active
but
delayed
Middle
East
in
infected
bronchial
epithelial
cells.
Studies
have
demonstrated
that
IFNs'
administration
before
viral
peak
inflammatory
phase
could
offer
highly
protective
effect.
However,
treatment
during
stages
causes
immunopathology
long-lasting
harm
patients.
Therefore,
it
is
critical
note
best
time
window
administration.
Further
investigation
clinical
effectiveness
patients
with
mild
COVID-19
its
optimal
timing
route
can
be
beneficial
finding
safe
therapy
disease.
The
2019
coronavirus
disease
(COVID-19)
pandemic
has
become
a
global
crisis.
In
the
immunopathogenesis
of
COVID-19,
SARS-CoV-2
infection
induces
an
excessive
inflammatory
response
in
patients,
causing
cytokine
storm
severe
cases.
Cytokine
leads
to
acute
respiratory
distress
syndrome,
pulmonary
and
other
multiorgan
failure,
which
is
important
cause
COVID-19
progression
even
death.
Among
them,
activation
pathways
major
factor
generating
storms
dysregulated
immune
responses,
closely
related
severity
viral
infection.
Therefore,
elucidation
signaling
pathway
providing
otential
therapeutic
targets
treatment
strategies
against
COVID-19.
Here,
we
discuss
pathogenesis
including
induction,
function,
downstream
signaling,
as
well
existing
potential
interventions
targeting
these
cytokines
or
pathways.
We
believe
that
comprehensive
understanding
regulatory
dysregulation
inflammation
will
help
develop
better
clinical
therapy
effectively
control
diseases,
such
Journal of Medical Virology,
Год журнала:
2022,
Номер
95(1)
Опубликована: Сен. 3, 2022
The
clinical
manifestation
of
coronavirus
disease
2019
(COVID-19)
mainly
targets
the
lung
as
a
primary
affected
organ,
which
is
also
critical
site
immune
cell
activation
by
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
However,
recent
reports
suggest
involvement
extrapulmonary
tissues
in
COVID-19
pathology.
interplay
both
innate
and
adaptive
responses
key
to
management.
As
result,
robust
response
provides
first
line
defense,
concomitantly,
immunity
neutralizes
infection
builds
memory
for
long-term
protection.
dysregulated
immunity,
adaptive,
can
skew
towards
immunopathology
chronic
cases.
Here
we
have
summarized
some
findings
that
provide
insight
into
caused
SARS-CoV-2,
post-acute
Finally,
further
discuss
immunomodulatory
drugs
preclinical
trials
dampening
COVID-19.
The Journal of Experimental Medicine,
Год журнала:
2022,
Номер
219(12)
Опубликована: Сен. 21, 2022
Severity
of
COVID-19
shows
an
extraordinary
correlation
with
increasing
age.
We
generated
a
mouse
model
for
severe
and
show
that
the
age-dependent
disease
severity
is
caused
by
disruption
timely
well-coordinated
innate
adaptive
immune
response
due
to
impaired
interferon
(IFN)
immunity.
Aggravated
in
aged
mice
was
characterized
diminished
IFN-γ
excessive
virus
replication.
Accordingly,
adult
receptor-deficient
phenocopied
age-related
severity,
supplementation
reversed
increased
susceptibility
mice.
Further,
we
therapeutic
treatment
IFN-λ
adults
combinatorial
Ifnar1−/−
highly
efficient
protecting
against
disease.
Our
findings
provide
explanation
clarify
nonredundant
antiviral
functions
type
I,
II,
III
IFNs
during
SARS-CoV-2
infection
manner.
data
suggest
vulnerable
individuals
could
benefit
from
immunotherapy
combining
IFN-λ.
PLoS Pathogens,
Год журнала:
2022,
Номер
18(10), С. e1010479 - e1010479
Опубликована: Окт. 24, 2022
Exacerbated
and
persistent
innate
immune
response
marked
by
pro-inflammatory
cytokine
expression
is
thought
to
be
a
major
driver
of
chronic
COVID-19
pathology.
Although
macrophages
are
not
the
primary
target
cells
SARS-CoV-2
infection
in
humans,
viral
RNA
antigens
activated
monocytes
have
been
detected
post-mortem
samples,
dysfunctional
hypothesized
contribute
protracted
hyper-inflammatory
state
patients.
In
this
study,
we
demonstrate
that
CD169,
myeloid
cell
specific
I-type
lectin,
facilitated
ACE2-independent
fusion
entry
macrophages.
CD169-mediated
resulted
genomic
subgenomic
RNAs
with
minimal
protein
no
infectious
particle
release,
suggesting
post-entry
restriction
replication
cycle.
Intriguingly
block
was
alleviated
exogenous
ACE2
Restricted
CD169
+
elicited
(TNFα,
IL-6
IL-1β)
RIG-I,
MDA-5
MAVS-dependent
manner,
which
suppressed
remdesivir
treatment.
These
findings
suggest
de
novo
contributes
signature
blocking
independent
subsequent
activation
might
alleviate
COVID-19-associated
hyperinflammatory
response.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(3), С. 2974 - 2974
Опубликована: Фев. 3, 2023
Coronavirus
disease-19
(COVID-19)
emerged
in
December
2019
and
quickly
spread,
giving
rise
to
a
pandemic
crisis.
Therefore,
it
triggered
tireless
efforts
identify
the
mechanisms
of
disease,
how
prevent
treat
it,
limit
hamper
its
global
dissemination.
Considering
above,
search
for
prophylactic
approaches
has
led
revolution
reglementary
pharmaceutical
pipeline,
with
approval
vaccines
against
COVID-19
an
unprecedented
way.
Moreover,
drug
repurposing
scheme
using
regulatory-approved
antiretroviral
agents
is
also
being
pursued.
However,
their
physicochemical
characteristics
or
reported
adverse
events
have
sometimes
limited
use.
Hence,
nanotechnology
been
employed
potentially
overcome
some
these
challenges,
particularly
cyclodextrins.
Cyclodextrins
are
cyclic
oligosaccharides
that
present
hydrophobic
cavities
suitable
complexing
several
drugs.
This
review,
besides
presenting
studies
on
inclusion
antiviral
drugs
cyclodextrins,
aims
summarize
currently
available
therapeutic
schemes
COVID-19,
highlighting
those
already
make
use
cyclodextrins
complexation.
In
addition,
new
underscored,
potential
application
increase
promising
will
be
addressed.
review
describes
instances
which
promotes
increased
bioavailability,
action,
solubility
under
analysis.
The
as
active
ingredient
covered.
Finally,
toxicity
regulatory
issues
well
future
perspectives
regarding
therapy
provided.
Journal of Medical Virology,
Год журнала:
2023,
Номер
95(4)
Опубликована: Март 17, 2023
Abstract
SARS‐CoV‐2
has
developed
a
variety
of
approaches
to
counteract
host
innate
antiviral
immunity
facilitate
its
infection,
replication
and
pathogenesis,
but
the
molecular
mechanisms
that
it
employs
are
still
not
been
fully
understood.
Here,
we
found
NSP8
inhibited
production
type
I
III
interferons
(IFNs)
by
acting
on
RIG‐I/MDA5
signaling
molecules
TRIF
STING.
Overexpression
downregulated
expression
IFNs
stimulated
poly
(I:C)
transfection
infection
with
SeV
SARS‐CoV‐2.
In
addition,
impaired
IFN
triggered
overexpression
RIG‐I,
MDA5,
MAVS,
instead
TBK1
IRF3‐5D,
an
active
form
IRF3.
From
mechanistic
view,
interacts
RIG‐I
thereby
prevents
assembly
RIG‐I/MDA5‐MAVS
signalosome,
resulting
in
phosphorylation
nuclear
translocation
also
suppressed
TRIF‐
STING‐
induced
directly
interacting
them.
Moreover,
ectopic
promoted
virus
replications.
Taken
together,
suppresses
responses
disturbing
RIG‐I/MDA5−MAVS
complex
formation
targeting
STING
transduction.
These
results
provide
new
insights
into
pathogenesis
COVID‐19.
