Animals,
Journal Year:
2023,
Volume and Issue:
13(7), P. 1210 - 1210
Published: March 30, 2023
Red
sea
bream
iridovirus
(RSIV)
causes
significant
economic
losses
in
aquaculture.
Here,
we
analyzed
the
pathogenicity,
viral
shedding,
and
transmission
dynamics
of
RSIV
rock
(Oplegnathus
fasciatus)
by
employing
immersion
infection
cohabitation
challenge
models.
Rock
challenged
exposure
exhibited
100%
mortality
within
35
days
post
exposure,
indicating
that
shedding
seawater
peaked
after
mortality.
At
25
°C,
a
positive
correlation
between
loads
infected
virus
into
was
observed.
Specific
lesions
were
observed
spleen
kidney
bream,
load
had
highest
with
histopathological
grade.
A
mimicking
natural
conditions
performed
to
assess
determine
pathogenicity
load.
The
RSIV-infected
breams
(donors)
cohabited
uninfected
red
(Pagrus
major),
flathead
grey
mullet
(Mugil
cephalus)
(recipients)
at
both
°C
15
°C.
In
group
maintained
no
across
all
experimental
groups.
However,
detected
recipient
fish.
Our
results
provide
preliminary
data
for
further
epidemiological
analyses
aid
development
preventive
measures
management
RSIVD
Med,
Journal Year:
2024,
Volume and Issue:
5(1), P. 42 - 61.e23
Published: Jan. 1, 2024
BackgroundOral
antiviral
drugs
with
improved
potency
and
safety
are
needed
to
address
current
challenges
in
clinical
practice
for
treatment
of
COVID-19,
including
the
risks
rebound,
drug-drug
interactions,
emerging
resistance.MethodsOlgotrelvir
(STI-1558)
is
designed
as
a
next-generation
targeting
SARS-CoV-2
main
protease
(Mpro),
an
essential
enzyme
replication,
human
cathepsin
L
(CTSL),
key
entry
into
host
cells.FindingsOlgotrelvir
highly
bioavailable
oral
prodrug
that
converted
plasma
its
active
form,
AC1115.
The
dual
mechanism
action
olgotrelvir
AC1115
was
confirmed
by
activity
inhibition
assays
co-crystal
structures
Mpro
CTSL.
displayed
inhibiting
replication
all
tested
variants
cell
culture
systems.
Olgotrelvir
also
inhibited
viral
cells
using
Spike-mediated
pseudotypes
In
K18-hACE2
transgenic
mouse
model
SARS-CoV-2-mediated
disease,
significantly
reduced
virus
load
lungs,
prevented
body
weight
loss,
cytokine
release
lung
pathologies.
demonstrated
potent
against
nirmatrelvir-resistant
E166
mutants.
showed
enhanced
bioavailability
animal
models
humans
significant
exposure
without
ritonavir.
phase
I
studies
(ClinicalTrials.gov:
NCT05364840
NCT05523739),
favorable
profile
activity.ConclusionsOlgotrelvir
inhibitor
CTSL
high
standalone
candidate
COVID-19.FundingFunded
Sorrento
Therapeutics.
Metabolites,
Journal Year:
2023,
Volume and Issue:
13(2), P. 309 - 309
Published: Feb. 20, 2023
The
nucleoside
analog
β-D-N4-hydroxycytidine
is
the
active
metabolite
of
prodrug
molnupiravir
and
accepted
as
an
efficient
drug
against
COVID-19.
Molnupiravir
targets
RNA-dependent
RNA
polymerase
(RdRp)
enzyme,
which
responsible
for
replicating
viral
genome
during
replication
process
certain
types
viruses.
It
works
by
disrupting
normal
function
RdRp
causing
it
to
make
mistakes
genome.
These
can
prevent
from
being
transcribed,
converted
into
a
complementary
DNA
template,
translated,
or
functional
protein.
By
these
crucial
steps
in
process,
effectively
inhibit
virus
reduce
its
ability
cause
disease.
This
review
article
sheds
light
on
impact
SARS-CoV-2
variants
concern,
such
delta,
omicron,
hybrid/recombinant
variants.
detailed
mechanism
molecular
interactions
using
docking
dynamics
have
also
been
covered.
safety
tolerability
patients
with
comorbidities
emphasized.
International Journal of Infectious Diseases,
Journal Year:
2023,
Volume and Issue:
133, P. 53 - 56
Published: May 5, 2023
Immunocompromised
patients
still
experience
unpredictable
courses
of
COVID-19,
despite
that
effective
vaccines
and
drugs
against
SARS-CoV-2
are
now
available.
Antiviral
combination
regimens
may
have
a
role
in
infection
immunocompromised
hosts,
but
current
knowledge
is
limited.
We
describe
the
case
73-year-old
Italian
man
affected
by
follicular
lymphoma
with
persistent
who
was
successfully
treated
co-administration
oral
antivirals
(10-day
molnupiravir
nirmatrelvir/ritonavir).
The
therapy
well
tolerated
both
from
clinical
biochemical
standpoint,
no
signs
toxicity.
also
performed
scoping
review,
to
sum
up
available
on
combined
antiviral
including
remdesivir,
molnupiravir,
or
nirmatrelvir/ritonavir.
Pending
further
studies
larger
cohorts
patients,
our
report
consistent
pre-clinical
data,
supporting
possible
use
selected
difficult-to-treat
COVID-19
cases.
Infection,
Journal Year:
2023,
Volume and Issue:
52(3), P. 877 - 889
Published: Nov. 29, 2023
Prolonged
shedding
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
has
been
observed
in
immunocompromised
hosts.
Early
monotherapy
with
direct-acting
antivirals
or
monoclonal
antibodies,
as
recommended
by
the
international
guidelines,
does
not
prevent
this
certainty.
Dual
therapies
may
therefore
have
a
synergistic
effect.
Clinical Microbiology Reviews,
Journal Year:
2024,
Volume and Issue:
37(2)
Published: May 21, 2024
SUMMARYSince
the
emergence
of
COVID-19
in
2020,
an
unprecedented
range
therapeutic
options
has
been
studied
and
deployed.
Healthcare
providers
have
multiple
treatment
approaches
to
choose
from,
but
efficacy
those
often
remains
controversial
or
compromised
by
viral
evolution.
Uncertainties
still
persist
regarding
best
therapies
for
high-risk
patients,
drug
pipeline
is
suffering
fatigue
shortage
funding.
In
this
article,
we
review
antiviral
activity,
mechanism
action,
pharmacokinetics,
safety
therapies.
Additionally,
summarize
evidence
from
randomized
controlled
trials
on
various
antivirals
discuss
unmet
needs
which
should
be
addressed.
Animal
models
of
COVID-19
facilitate
the
development
vaccines
and
antivirals
against
SARS-CoV-2.
The
efficacy
or
may
differ
in
different
animal
with
varied
degrees
disease.
Here,
we
introduce
a
mouse
model
expressing
human
angiotensin-converting
enzyme
2
(ACE2).
In
this
model,
