RSC Advances,
Journal Year:
2023,
Volume and Issue:
13(50), P. 35500 - 35524
Published: Jan. 1, 2023
The
pandemic
caused
by
the
coronavirus
SARS-CoV-2
led
to
a
global
crisis
in
world
healthcare
system.
Despite
some
progress
creation
of
antiviral
vaccines
and
mass
vaccination
population,
number
patients
continues
grow
because
spread
new
mutations.
There
is
an
urgent
need
for
direct-acting
drugs
capable
suppressing
or
stopping
main
mechanisms
reproduction
SARS-CoV-2.
Several
studies
have
shown
that
successful
replication
virus
cell
requires
proteolytic
cleavage
protein
structures
virus.
Two
proteases
are
crucial
replicating
other
coronaviruses:
protease
(Mpro)
papain-like
(PLpro).
In
this
review,
we
summarize
essential
viral
proteins
required
its
life
cycle
as
targets
chemotherapy
infection
provide
critical
summary
development
against
COVID-19
from
drug
repurposing
strategy
up
molecular
design
novel
covalent
non-covalent
agents
inhibiting
replication.
We
overview
choice
Mpro
PLpro
promising
pharmacological
impact
on
cycle.
Nature Microbiology,
Journal Year:
2024,
Volume and Issue:
9(4), P. 1075 - 1088
Published: March 29, 2024
Abstract
Although
vaccines
are
available
for
SARS-CoV-2,
antiviral
drugs
such
as
nirmatrelvir
still
needed,
particularly
individuals
in
whom
less
effective,
the
immunocompromised,
to
prevent
severe
COVID-19.
Here
we
report
an
α-ketoamide-based
peptidomimetic
inhibitor
of
SARS-CoV-2
main
protease
(M
pro
),
designated
RAY1216.
Enzyme
inhibition
kinetic
analysis
shows
that
RAY1216
has
constant
8.4
nM
and
suggests
it
dissociates
about
12
times
slower
from
M
compared
with
nirmatrelvir.
The
crystal
structure
:RAY1216
complex
covalently
binds
catalytic
Cys145
through
α-ketoamide
group.
In
vitro
using
human
ACE2
transgenic
mouse
models,
activities
against
variants
comparable
those
It
also
improved
pharmacokinetics
mice
rats,
suggesting
could
be
used
without
ritonavir,
which
is
co-administered
been
approved
a
single-component
drug
named
‘leritrelvir’
COVID-19
treatment
China.
Results in Engineering,
Journal Year:
2023,
Volume and Issue:
19, P. 101335 - 101335
Published: Aug. 1, 2023
As
an
important
theoretical
computation
method
in
computer-aided
drug
design,
molecular
docking
has
significantly
shifted
the
paradigm
of
discovery.
one
open-source
software,
Autodock
Vina
(Vina)
is
widely
popular,
but
lack
relevant
experience
and
inappropriate
parameters
make
it
unable
to
perform
optimally
practical
application
scenarios,
which
leads
potential
failure
risks
early
stage
In
order
simplify
steps
determine
most
appropriate
parameters,
a
universal
solution
for
rigid
receptor
using
been
proposed
this
paper,
user-friendly
software
entire
process
developed.
The
case
studies
show
that
our
able
be
applied
different
scenarios
facilitate
more
accurate,
faster,
convenient
new
discovery
process.
Biomolecules,
Journal Year:
2023,
Volume and Issue:
13(9), P. 1339 - 1339
Published: Sept. 2, 2023
The
main
protease
(Mpro)
plays
a
pivotal
role
in
the
replication
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
and
is
considered
highly
conserved
viral
target.
Disruption
catalytic
activity
Mpro
produces
detrimental
effect
on
course
infection,
making
this
target
one
most
attractive
for
treatment
COVID-19.
current
success
SARS-CoV-2
inhibitor
Nirmatrelvir,
first
oral
drug
forms
COVID-19,
has
further
focused
attention
researchers
important
target,
search
new
inhibitors
thriving
exciting
field
development
antiviral
drugs
active
against
related
coronaviruses.
ACS Medicinal Chemistry Letters,
Journal Year:
2024,
Volume and Issue:
15(2), P. 250 - 257
Published: Jan. 10, 2024
We
have
applied
a
proteolysis
targeting
chimera
(PROTAC)
technology
to
obtain
peptidomimetic
molecule
able
trigger
the
degradation
of
SARS-CoV-2
3-chymotrypsin-like
protease
(3CLPro).
The
PROTAC
was
designed
by
conjugating
GC-376
based
dipeptidyl
3CLPro
ligand
pomalidomide
moiety
through
piperazine–piperidine
linker.
NMR
and
crystallographic
data
complemented
with
enzymatic
cellular
studies
showed
that
(i)
binds
active
site
dimeric
state
forming
reversible
covalent
bond
sulfur
atom
catalytic
Cys145,
(ii)
linker
cereblon-ligand
protrude
from
protein,
displaying
high
degree
flexibility
no
interactions
other
regions
(iii)
reduces
protein
levels
in
cultured
cells.
This
study
paves
way
for
future
applicability
PROTACs
tackle
3CLPro-dependent
viral
infections.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 2, 2025
Variants
of
SARS-CoV-2
have
continued
to
emerge
across
the
world
and
cause
hundreds
deaths
each
week.
Due
limited
efficacy
vaccines
against
resistance
current
therapies,
additional
anti-viral
therapeutics
with
pan-coronavirus
activity
are
high
interest.
Here,
we
screen
2.8
billion
compounds
from
a
DNA-encoded
chemical
library
identify
small
molecules
that
non-covalent
inhibitors
targeting
conserved
3CL
protease
other
coronaviruses.
We
perform
structure-based
optimization,
leading
creation
series
potent,
inhibitors,
for
coronavirus
infections.
To
characterize
their
binding
mechanism
protease,
determine
16
co-crystal
structures
find
optimized
specifically
interact
both
protomers
native
homodimer
protease.
Since
is
catalytically
competent
only
in
dimeric
state,
these
data
provide
insight
into
design
drug-like
state.
With
mode
different
covalent
inhibitor
nirmatrelvir,
COVID
drug
Paxlovid,
may
overcome
reported
nirmatrelvir
complement
its
clinical
utility.
therapies
authors
screened
identified
