Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial
Clinical Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 20, 2025
Ensitrelvir,
a
severe
acute
respiratory
syndrome
coronavirus-2
main
protease
inhibitor,
has
demonstrated
clinical
and
virologic
efficacy
in
previous
studies.
In
this
global
phase
3
trial,
nonhospitalized
adults
with
mild-to-moderate
coronavirus
disease
2019
(COVID-19)
symptom
onset
within
5
days
were
randomized
(1:1)
to
receive
once-daily
ensitrelvir
(375
mg
day
1,
125
2-5)
or
blinded
matching
placebo.
The
primary
endpoint
was
the
restricted
mean
time
sustained
(≥2
days)
resolution
of
15
COVID-19
symptoms,
recorded
participant
daily
diaries,
through
29
participants
starting
treatment
after
onset.
Virologic
safety
assessed.
Of
2093
participants,
1888
started
Mean
12.5
13.1
placebo,
respectively
(difference,
-0.6
days;
95%
confidence
interval,
-1.38
0.19;
P
=
.14).
On
4,
reduced
least-squares
RNA
by
0.72
log10
copies/mL
more
than
placebo
(95%
0.55-0.90).
Among
those
positive
viral
cultures
at
enrollment,
274/287
(95.5%)
ensitrelvir-treated
versus
210/280
(75.0%)
placebo-treated
had
negative
on
4.
rebound
similar
(<1.5%)
between
groups.
proportion
≥1
adverse
event
(61.5%)
(60.6%).
No
treatment-related
serious
events
deaths
occurred.
Three
(0.3%)
1
(0.1%)
COVID-19-related
hospitalizations
29.
Despite
evidence
antiviral
activity
ensitrelvir,
trial
did
not
demonstrate
significant
difference
resolution.
Язык: Английский
mRNA vaccine platforms: linking infectious disease prevention and cancer immunotherapy
Frontiers in Bioengineering and Biotechnology,
Год журнала:
2025,
Номер
13
Опубликована: Март 12, 2025
The
advent
of
mRNA
vaccines,
accelerated
by
the
global
response
to
COVID-19
pandemic,
marks
a
transformative
shift
in
vaccine
technology.
In
this
article,
we
discuss
development,
current
applications,
and
prospects
vaccines
for
both
prevention
treatment
infectious
diseases
oncology.
By
leveraging
capacity
encode
antigens
within
host
cells
directly,
provide
versatile
scalable
platform
suitable
addressing
broad
spectrum
pathogens
tumor-specific
antigens.
We
highlight
recent
advancements
design,
innovative
delivery
mechanisms,
ongoing
clinical
trials,
with
particular
emphasis
on
their
efficacy
combating
diseases,
such
as
COVID-19,
Zika,
influenza,
well
emerging
potential
cancer
immunotherapy.
also
address
critical
challenges,
including
stability,
optimization
immune
responses,
broader
issue
accessibility.
Finally,
review
strategies
advancing
next-generation
aim
overcoming
limitations
technology
enhancing
preventive
therapeutic
approaches
oncological
diseases.
Язык: Английский
12-month persistence of immune responses to self-amplifying mRNA COVID-19 vaccines: ARCT-154 versus BNT162b2 vaccine
The Lancet Infectious Diseases,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 1, 2024
Язык: Английский
Comparative Study of Ensitrelvir and Symptomatic Therapy in Healthcare Workers with Mild COVID-19: A Single Center Retrospective Analysis in Chiba, Japan.
Journal of Infection and Chemotherapy,
Год журнала:
2025,
Номер
unknown, С. 102668 - 102668
Опубликована: Фев. 1, 2025
Язык: Английский
Genomic epidemiology and evolutionary dynamics of the Omicron variant of SARS-CoV-2 during the fifth wave of COVID-19 in Pakistan
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2024,
Номер
14
Опубликована: Окт. 22, 2024
Introduction
The
coronavirus
disease
2019
(COVID-19)
pandemic,
caused
by
severe
acute
respiratory
syndrome
2
(SARS-CoV-2),
has
posed
extraordinary
challenges
to
global
health
systems
and
economies.
virus’s
rapid
evolution
resulted
in
several
variants
of
concern
(VOCs),
including
the
highly
transmissible
Omicron
variant,
characterized
extensive
mutations.
In
this
study,
we
investigated
genetic
diversity,
population
differentiation,
evolutionary
dynamics
VOC
during
fifth
wave
COVID-19
Pakistan.
Methods
A
total
954
genomes
sequenced
Pakistan
were
analyzed.
Bayesian
framework
was
employed
for
phylogenetic
reconstructions,
molecular
dating,
analysis.
Results
Using
a
genomics
approach,
analyzed
Pakistani
samples,
revealing
low
within-population
diversity
significant
structural
variation
spike
(S)
protein.
Phylogenetic
analysis
showed
that
variant
originated
from
two
distinct
lineages,
BA.1
BA.2,
which
introduced
South
Africa,
Thailand,
Spain,
Belgium.
Omicron-specific
mutations,
those
receptor-binding
domain,
identified.
estimated
rate
2.562E-3
mutations
per
site
year
(95%
HPD
interval:
8.8067E-4
4.1462E-3).
skyline
plot
indicated
expansion
at
end
2021,
coinciding
with
outbreak.
Comparative
other
VOCs
as
divergent,
monophyletic
group,
suggesting
unique
pathway.
Conclusions
This
study
provides
comprehensive
overview
Omicron’s
genomic
epidemiology,
Pakistan,
emphasizing
need
collaboration
monitoring
enhancing
pandemic
preparedness.
Язык: Английский
Thiol-Reactive or Redox-Active: Revising a Repurposing Screen Led to a New Invalidation Pipeline and Identified a True Noncovalent Inhibitor Against Papain-like Protease from SARS-CoV-2
ACS Pharmacology & Translational Science,
Год журнала:
2024,
Номер
8(1), С. 66 - 77
Опубликована: Окт. 4, 2024
The
SARS-CoV-2
papain-like
protease
PLpro
has
multiple
roles
in
the
viral
replication
cycle,
related
to
both
its
polypeptide
cleavage
function
and
ability
antagonize
host
immune
response.
Targeting
is
recognized
as
a
promising
mechanism
modulate
replication,
while
supporting
responses.
However,
development
of
PLpro-specific
inhibitors
remains
challenging.
Comprehensive
investigations
utilizing
enzymatic,
binding
studies,
cellular
assays
revealed
previously
reported
act
an
unspecific
manner.
At
present,
GRL-0617
derivatives
remain
best-validated
compounds
with
demonstrated
antiviral
activity
cells
mouse
models.
In
this
study,
we
refer
pitfalls
redox
sensitivity
PLpro.
Using
screening-based
approach
identify
PLpro's
proteolytic
activity,
made
extensive
efforts
validate
active
over
range
conditions
readouts,
emphasizing
need
for
comprehensive
orthogonal
data
when
profiling
putative
inhibitors.
remaining
compound,
CPI-169,
was
shown
be
noncovalent
inhibitor
capable
competing
NMR-based
experiments,
suggesting
that
it
occupied
similar
site
inhibited
Vero-E6
cells,
opening
new
design
opportunities
further
agents.
Язык: Английский