Comprehensive screening, separation, extraction optimization, and bioactivity evaluation of xanthine oxidase inhibitors from Ganoderma leucocontextum
Arabian Journal of Chemistry,
Год журнала:
2025,
Номер
0, С. 1 - 14
Опубликована: Апрель 11, 2025
Язык: Английский
Repurposing FDA-Approved Drugs as Potential Inhibitors of SARS-CoV-2 PLpro: A Comprehensive Computational Study
Journal of Computational Biophysics and Chemistry,
Год журнала:
2024,
Номер
23(09), С. 1209 - 1231
Опубликована: Авг. 1, 2024
This
study
explores
the
repurposing
of
Food
and
Drug
Administration
(FDA)-approved
drugs
as
potential
inhibitors
SARS-CoV-2
papain-like
protease
(PLpro),
a
critical
enzyme
for
viral
replication.
Initially,
3009
FDA
approved
were
screened
to
identify
candidates
structurally
similar
co-crystallized
ligand
XT7
in
PLpro
complex
(PDB
ID:
7LBR).
A
fingerprint
analysis
narrowed
selection
top
5%
)150
drugs)
most
akin
XT7,
followed
by
more
refined
structural
similarity
test
that
identified
1%
(30
drugs).
Molecular
docking
studies
highlighted
several
compounds
with
strong
binding
affinities
PLpro.
Notably,
Fedratinib
exhibited
particularly
robust
energy
[Formula:
see
text]kcal/mol
was
chosen
further
investigation.
Subsequent
molecular
dynamics
(MD)
simulations
over
100
ns
confirmed
stability
efficacy
Fedratinib’s
binding,
evidenced
favorable
energetic
dynamic
profiles.
The
mechanics-generalized
born
surface
area
(MM-GBSA)
calculations
corroborated
these
findings,
revealing
text]kcal/mol.
Additionally,
PLIP,
ProLIF,
PCAT
analyses
validated
interactions
PLpro-Fedratinib
observed
during
MD
simulations.
Overall,
our
results
indicate
Fedratinib,
an
FDA-approved
drug,
demonstrates
promising
inhibitor
PLpro,
warranting
vitro
vivo
experimental
validation
well
clinical
evaluation.
Язык: Английский
Repurposing FDA-approved drugs for COVID-19: targeting the main protease through multi-phase in silico approach
Antiviral Therapy,
Год журнала:
2024,
Номер
29(6)
Опубликована: Дек. 1, 2024
Background
The
COVID-19
pandemic
has
created
an
urgent
need
for
effective
therapeutic
agents.
SARS-CoV-2
Main
Protease
(M
pro
)
plays
a
crucial
role
in
viral
replication
and
immune
evasion,
making
it
key
target
drug
development.
While
several
studies
have
explored
M
inhibition,
identifying
FDA-approved
drugs
with
potential
efficacy
remains
critical
research
focus.
Purpose
This
study
aims
to
identify
that
could
inhibit
.
Using
computational
screening,
we
seek
compounds
share
structural
similarities
known
co-crystallized
ligand
(PRD_002214)
exhibit
strong
binding
affinity
the
enzyme,
providing
viable
candidates
treatment.
Research
Design
A
systematic
silico
approach
was
used,
screening
3009
drugs.
initial
focused
on
similarity
PRD_002214
(PDB
ID:
6LU7),
followed
by
molecular
docking
predict
affinity.
Promising
were
further
analyzed
through
dynamics
(MD)
simulations
evaluate
their
stability
interactions
over
100
ns.
Study
Sample
Of
screened,
74
selected
evaluation.
After
refinement,
28
underwent
analysis,
eight
showing
Analysis
Molecular
assessed
interaction
of
MD
conducted
top
compound,
Atazanavir,
its
dynamic
interactions.
MM-GBSA,
PLIP,
PCAT
analyses
used
validate
Results
Eight
compounds,
including
Carfilzomib,
Darunavir,
others,
exhibited
promising
affinities.
Among
them,
Atazanavir
showed
highest
strength
simulation
studies.
These
revealed
forms
stable
,
demonstrating
favorable
stability.
confirmed
analyses,
supporting
Atazanavir's
as
inhibitor.
Conclusions
In
results
suggest
is
candidate
targeting
findings
support
lead
compound
preclinical
clinical
testing,
though
vitro
vivo
validation
are
needed
confirm
against
COVID-19.
Язык: Английский
Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and In vitro assays
PLoS ONE,
Год журнала:
2024,
Номер
19(12), С. e0312866 - e0312866
Опубликована: Дек. 3, 2024
To
find
an
effective
inhibitor
for
SARS-CoV-2,
Quercetin’s
chemical
structure
was
compared
to
nine
ligands
associated
with
key
SARS-CoV-2
proteins.
It
found
that
Quercetin
closely
resembles
Remdesivir,
the
co-crystallized
ligand
of
RNA-dependent
RNA
polymerase
(RdRp).
This
similarity
confirmed
through
flexible
alignment
experiments
and
molecular
docking
studies,
which
showed
both
Remdesivir
bind
similarly
active
site
RdRp.
Molecular
dynamics
(MD)
simulations
over
a
200
ns
trajectory,
analyzing
various
factors
like
RMSD,
RG,
RMSF,
SASA,
hydrogen
bonding
were
conducted.
These
gave
detailed
insights
into
binding
interactions
RdRp
Remdesivir.
Further
analyses,
including
MM-GBSA,
Protein-Ligand
Interaction
Fingerprints
(ProLIF)
Profile
PLIP
stability
binding.
Principal
component
analysis
trajectories
(PCAT)
provided
coordinated
movements
within
systems
studied.
In
vitro
assays
is
highly
in
inhibiting
RdRp,
IC
50
122.1
±5.46
nM,
better
than
Remdesivir’s
21.62
±2.81
μM.
Moreover,
greater
efficacy
against
,
1.149
μg/ml
9.54
μg/ml.
The
selectivity
index
(SI)
values
highlighted
safety
margin
(SI:
791)
6).
conclusion,
our
comprehensive
study
suggests
promising
candidate
further
research
as
providing
valuable
developing
anti-COVID-19
treatment.
Язык: Английский