International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(17), С. 13491 - 13491
Опубликована: Авг. 30, 2023
The
severe
acute
respiratory
syndrome-causing
coronavirus
2
(SARS-CoV-2)
papain-like
protease
(PLpro)
and
main
(Mpro)
play
an
important
role
in
viral
replication
events
are
targets
for
anti-coronavirus
drug
discovery.
In
search
of
these
inhibitors,
we
screened
a
library
1300
compounds
using
fluorescence
thermal
shift
assay
(FTSA)
identified
53
hits
that
thermally
stabilized
or
destabilized
PLpro.
hit
structurally
belonged
to
two
classes
small
molecules:
thiazole
derivatives
symmetrical
disulfide
compounds.
Compound
dissociation
constants
(Kd)
were
determined
enzymatic
inhibition
method.
Seven
aromatic
as
efficient
PLpro
inhibitors
with
Kd
values
the
micromolar
range.
Two
disulfides
displayed
six-fold
higher
potency
(Kd
=
0.5
µM)
than
Mpro.
bound
covalently
both
proteases,
confirmed
through
mass
spectrometry.
can
serve
lead
further
chemical
optimization
toward
anti-COVID-19
drugs.
Communications Biology,
Год журнала:
2024,
Номер
7(1)
Опубликована: Сен. 17, 2024
Toll-like
receptor
7
(Tlr7)
deficiency-accelerated
severe
COVID-19
is
associated
with
reduced
production
of
interferons
(IFNs).
However,
the
underlying
mechanisms
remain
elusive.
To
address
these
questions,
we
utilize
Tlr7
and
Irf7
deficiency
mice,
single-cell
RNA
analysis
together
bone
marrow
transplantation
approaches.
We
demonstrate
that
at
early
phase
infection,
SARS-CoV-2
causes
upregulation
Tlr7,
Irf7,
IFN
pathways
in
lungs
infected
mice.
The
globally
and/or
immune
cells
mice
increases
severity
via
impaired
activation
both
non-immune
cells,
leading
to
increased
lung
viral
loads.
These
effects
are
alpha
gamma
levels
circulation.
tends
cause
nuclear
translocation
interferon
regulatory
factor
(IRF7)
indicative
IRF7
activation.
Despite
higher
amounts
antigen,
or
resulted
substantially
antibodies
against
SARS-CoV-2,
thereby
delaying
clearance.
results
highlight
importance
TLR7
on
development
innate
adaptive
immunity
COVID-19.
Health Science Reports,
Год журнала:
2024,
Номер
7(11)
Опубликована: Ноя. 1, 2024
There
is
a
demand
for
additional
data
regarding
the
impact
of
coronavirus
disease
2019
(COVID-19)
on
pediatric
population.
This
study
sought
to
determine
clinical
and
epidemiological
features
COVID-19
in
Iran.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(17), С. 13491 - 13491
Опубликована: Авг. 30, 2023
The
severe
acute
respiratory
syndrome-causing
coronavirus
2
(SARS-CoV-2)
papain-like
protease
(PLpro)
and
main
(Mpro)
play
an
important
role
in
viral
replication
events
are
targets
for
anti-coronavirus
drug
discovery.
In
search
of
these
inhibitors,
we
screened
a
library
1300
compounds
using
fluorescence
thermal
shift
assay
(FTSA)
identified
53
hits
that
thermally
stabilized
or
destabilized
PLpro.
hit
structurally
belonged
to
two
classes
small
molecules:
thiazole
derivatives
symmetrical
disulfide
compounds.
Compound
dissociation
constants
(Kd)
were
determined
enzymatic
inhibition
method.
Seven
aromatic
as
efficient
PLpro
inhibitors
with
Kd
values
the
micromolar
range.
Two
disulfides
displayed
six-fold
higher
potency
(Kd
=
0.5
µM)
than
Mpro.
bound
covalently
both
proteases,
confirmed
through
mass
spectrometry.
can
serve
lead
further
chemical
optimization
toward
anti-COVID-19
drugs.
