Abstract
In
recent
years,
Vortioxetine
derivatives
have
attracted
much
attention
as
main
protease
inhibitors
of
SARS‐CoV‐2.
this
study,
the
structure‐activity
relationship
32
was
studied
by
CoMFA
and
CoMSIA
models.
The
results
show
that
(q
2
=0.522,
r
=0.996)
=0.562,
=0.934)
good
estimation
stability
prediction
ability.
Subsequently,
through
analysis
3D‐QSAR
model,
we
designed
four
novel
compounds,
verified
pharmacokinetic
properties
new
molecules
were
superior
to
compound
28
ADMET,
key
amino
acid
action
sites
molecule
molecular
docking.
Finally,
compared
with
dynamics
simulation
MMPBSA,
which
further
efficacy
,
wherein
binding
free
energy
N1
(ΔG=−161.38
kJ/mol)>N4
(ΔG=−154.19
kJ/mol)>C28
(ΔG=−129.13
kJ/mol),
indicating
newly
drug
are
more
suitable
for
subsequent
experimental
verification.
findings
presented
herein
can
offer
valuable
guidance
design
development
efficacious
innovative
targeting
SARS‐CoV‐2
protease.
Frontiers in Microbiology,
Год журнала:
2022,
Номер
13
Опубликована: Июль 13, 2022
Berberine
hydrochloride
(BBR)
is
a
natural
product
widely
used
in
clinical
medicine
and
animal
production.
It
has
variety
of
antimicrobial
effects,
but
its
complex
mechanism
not
been
clarified.
This
study
aimed
to
discover
the
metabolic
markers
gain
new
perspective
on
antibacterial
BBR.
The
effects
different
inhibitory
concentrations
BBR
survival
growth
standard
strain
Staphylococcus
aureus
ATCC
25923
were
analyzed
by
bacteriostatic
activity
test.
Differences
intracellular
metabolites
S.
following
19
μg/ml
exposure
for
1
h
investigated
combining
non-targeted
metabolomics
techniques
gas
chromatography-mass
spectrometry
(GC-MS)
liquid
(LC-MS).
results
showed
that
minimum
concentration
against
was
51
μg/ml.
A
total
368
3,454
putative
identified
GC-MS
LC-MS
analyses,
respectively.
Principal
component
analysis
separation
metabolite
profiles
between
BBR-exposed
samples
non-exposed
controls.
Pathway
profiling
indicated
global
inhibition
metabolisms
exposure,
while
enhancement
also
found
nucleic
acid
metabolism,
amino
sugar,
nucleotide
sugar
metabolism.
Several
screened
out
mainly
based
their
variable
importance
projection
values.
Two
pyridine
dicarboxylic
acids
significantly
downregulated,
suggesting
reduction
stress
resistance.
oxidized
phospholipid
(PHOOA-PE)
accumulated,
lipid
antioxidant
gamma-tocopherol
decreased,
farnesyl
PP,
synthetic
precursor
another
(staphyloxanthin),
decreased
below
detection
threshold.
evidence
indicates
reduced
capacity
aureus.
Accumulation
precursors
(UDP-GlcNAc,
CDP-ribitol,
CDP-glycerol)
downregulation
key
D-Ala-D-Ala
suggest
cell
wall
synthesis,
especially
peptidoglycan
synthesis.
Metabolites
involved
shikimate
pathway
(such
as
3-dehydroshikimate)
downstream
aromatic
synthesis
disturbed.
provides
first
information
this
pathway,
staphyloxanthin
biosynthesis
are
directions
further
future.
Abstract
The
bioactivity
of
phytochemicals
has
been
widely
reported
in
the
literature,
however,
abundance
phytochemical
resources
and
their
potent
activities
require
laborious
screening
methods
for
feasible
applications.
Owing
to
lack
pharmacologically
safe
therapeutic
options
tackle
emerging
infections
drug
resistance,
there
is
an
increasing
interest
diverse
potential
bioactive
phytochemicals.
However,
consolidated
reports
on
same
are
very
limited.
present
article
provides
overview
exemplary
studies
from
last
decade
application
silico
that
have
guided
fast
efficient
domain
pertains
functional
aspects
phytochemicals,
such
as
antibacterial,
antiviral,
antiparasitic,
antifungal,
antioxidant,
anti-inflammatory,
anticancer
effects.
Based
reviewed
computational
approaches,
a
common
popularly
adopted
pipeline
was
illustrated
utility
A
list
databases
provided
help
researchers
identify
phytocompounds
research.
prospect
generating
high
volume
research
data
can
facilitate
machine
learning
artificial
intelligence-based
future
predictions
during
healthcare
emergencies
disease
outbreaks.
Journal of Biomolecular Structure and Dynamics,
Год журнала:
2023,
Номер
42(18), С. 9294 - 9308
Опубликована: Авг. 28, 2023
AbstractThe
current
work
describes
a
fragment
linking
methodology
to
generate
new
neuraminidase
inhibitors.
A
total
number
of
28,977
fragments
from
Zinc
20
have
been
obtained
and
screened
for
receptor
affinity.
Using
Schrödinger
software,
the
highest-scoring
270
hits
(with
scores
greater
than
−7.6)
were
subjected
combining
create
100
molecules.
These
novel
compounds
studied
using
XP
docking
evaluate
molecular
interaction
modes
their
binding
affinity
receptor.
The
top
ten
molecules
selected,
ADMET,
drug-likeness
features.
Based
on
these
characteristics,
best
four
developed
Zanamivir
submitted
dynamics
simulation
investigation
estimate
within
Gromacs
software.
All
MD
findings
show
that
generated
complexes
are
very
stable
when
compared
clinical
inhibitor
(Zanamivir).
In
addition,
designed
inhibitors
formed
with
energies
ranging
−83.50
−107.85
Kj/mol)
according
energy
calculated
by
MM-PBSA.
For
objective
developing
influenza
medications,
potential
be
further
evaluated
in
vitro
vivo
drug
discovery.Communicated
Ramaswamy
H.
SarmaKeywords:
Influenzaneuraminidase
inhibitorsfragment-based
designmolecular
dockingADMETmolecular
dynamicsMM-PBSAgromacs
Disclosure
statementNo
conflict
interest
was
reported
author(s).Additional
informationFundingThe
author(s)
there
is
no
funding
associated
featured
this
article.
Chemistry & Biodiversity,
Год журнала:
2024,
Номер
21(5)
Опубликована: Март 25, 2024
The
SARS-CoV-2
main
protease,
as
a
key
target
for
antiviral
therapeutics,
is
instrumental
in
maintaining
virus
stability,
facilitating
translation,
and
enabling
the
to
evade
innate
immunity.
Our
research
focused
on
designing
non-covalent
inhibitors
counteract
action
of
this
protease.
Utilizing
3D-QSAR
model
contour
map,
we
successfully
engineered
eight
novel
inhibitors.
Further
evaluation
comparison
these
compounds
through
methodologies
including
molecular
docking,
ADMET
analysis,
frontier
orbital
studies,
dynamics
simulations,
binding
free
energy
revealed
that
N02
N03
demonstrated
superior
performance
(N02
ΔG
