Identification of promising SARS-CoV-2 main protease inhibitor through molecular docking, dynamics simulation, and ADMET analysis
Scientific Reports,
Journal Year:
2025,
Volume and Issue:
15(1)
Published: Jan. 22, 2025
Abstract
The
COVID-19
pandemic
caused
by
SARS-CoV-2
continues
to
pose
a
major
challenge
global
health.
Targeting
the
main
protease
of
virus
(Mpro),
which
is
essential
for
viral
replication
and
transcription,
offers
promising
approach
therapeutic
intervention.
In
this
study,
advanced
computational
techniques
such
as
molecular
docking
dynamics
simulations
were
used
screen
series
antiviral
compounds
their
potential
inhibitory
effect
on
Mpro.
A
comprehensive
analysis
from
ChemDiv
PubChem
databases
was
performed.
physicochemical
properties,
pharmacokinetics,
ADMET
(Absorption,
Distribution,
Metabolism,
Excretion,
Toxicity)
profiles
evaluated
determine
drug
similarity
safety.
Compound
4896
−
4038
proved
be
most
candidate.
It
exhibited
favorable
balance
between
weight
(491.06)
lipophilicity
(logP
3.957),
high
intestinal
absorption
(92.119%),
broad
tissue
distribution
(VDss
0.529),
indicating
good
oral
bioavailability
potential.
Molecular
studies
showed
that
has
strong
binding
affinity
active
site
Mpro
forms
key
interactions,
hydrogen
bonds,
carbon-hydrogen
pi-sulfur,
multiple
van
der
Waals
pi-pi
stacked
bonds.
energy
comparable
reference
X77,
efficacy.
over
300
ns
confirmed
stability
Mpro/4896
complex
protein-ligand.
Free
landscape
mapping
MM/PBSA
calculations
further
substantiated
complex.
Importantly,
comparatively
safety
profile.
summary,
compound
shows
significant
potent
inhibitor,
combining
activity
with
pharmacokinetic
profiles.
These
results
support
development
agent
in
fight
against
warrants
experimental
validation
clinical
investigation.
Language: Английский
Docking and Post-Processing of 1 Million Molecules from the CNCL Database in Search of SARS-CoV-2 Mpro Inhibitors
Lecture notes in computer science,
Journal Year:
2025,
Volume and Issue:
unknown, P. 47 - 58
Published: Jan. 1, 2025
Language: Английский
In Silico and In Vitro Studies of the Approved Antibiotic Ceftaroline Fosamil and Its Metabolites as Inhibitors of SARS-CoV-2 Replication
Viruses,
Journal Year:
2025,
Volume and Issue:
17(4), P. 491 - 491
Published: March 28, 2025
The
SARS-CoV-2
proteases
Mpro
and
PLpro
are
critical
targets
for
antiviral
drug
development
the
treatment
of
COVID-19.
1,2,4-thiadiazole
functional
group
is
an
inhibitor
cysteine
proteases,
such
as
papain
cathepsins.
This
chemical
moiety
also
present
in
ceftaroline
fosamil
(CF),
FDA-approved
fifth-generation
cephalosporin
antibiotic.
study
investigates
interactions
between
CF,
its
primary
metabolites
(M1
dephosphorylated
CF
M2
opened
β-lactam
ring)
derivatives
(protonated
M1H
M2H),
open
rings
(open-M1H
open-M2H)
with
evaluates
CF’s
effects
on
vitro
viral
replication.
In
silico
analyses
(molecular
docking
molecular
dynamics
(MD)
simulations)
demonstrated
that
potential
inhibitors
Mpro.
Docking
analysis
indicated
majority
ligands
were
more
stable
than
PLpro;
however,
biochemical
preferred
target
CF.
inhibited
replication
human
Calu-3
cell
model
at
submicromolar
concentrations
when
added
to
culture
medium
12
h.
Our
results
suggest
should
be
evaluated
a
repurposing
agent
COVID-19,
considering
not
only
but
other
relevant
cellular
pathways.
Additionally,
reactivity
sulfur
warrants
further
exploration
protease
inhibitors.
Language: Английский
The Application of Computer-Aided Drug Design Technology in Drug Development
Menghan Cui
No information about this author
Published: Aug. 13, 2024
Language: Английский
Pyrrolizines: natural and synthetic derivatives with diverse biological activities
International Journal of Clinical Medical Research,
Journal Year:
2024,
Volume and Issue:
2(5), P. 171 - 184
Published: Sept. 17, 2024
The
pyrrolizine
nucleus
is
a
bicyclic
ring
system
that
consists
of
pyrrole
fused
to
another
pyrrolidin
ring.
It
constitutes
the
basic
skeleton
in
many
natural
and
synthetic
compounds
with
diverse
biological
activities
such
as
anti-inflammatory,
nootropic,
antiemetic,
antibacterial,
antiviral,
anticonvulsant,
antiarrhythmic,
anticancer
activities.
At
least
two
these
derivatives,
ketorolac
mitomycin
C,
have
been
approved
for
treatment
inflammation
cancer,
respectively.
Licofelone,
dual
inhibitor
COX
5-LOX,
was
also
evaluated
clinical
trials
osteoarthritis.
On
other
hand,
large
number
pyrrolizine-based
derivatives
displayed
activity
against
different
types
cancer
cells.
In
this
review,
were
classified
based
on
their
chemical
structure
into
substituted,
fused,
spiro-pyrrolizine.
mechanisms
action
included
alkylation
DNA,
inhibition
COX,
or
alteration
permeability
cytoplasmic
membrane
addition,
pyrrolizines
found
act
by
inhibiting
DNA
replication,
rRNA,
Rac1
kinase,
thioredoxin
reductase,
oncogenic
kinases.
last
section
review
focuses
reported
X-ray
crystal
structures
proteins.
binding
modes
interactions
licofelone
illustrated
review.
To
sum
up,
we
anticipate
data
compiled
will
be
useful
researchers
design
potent
Language: Английский