The Design, Synthesis and Mechanism of Action of Paxlovid, a Protease Inhibitor Drug Combination for the Treatment of COVID-19
Pharmaceutics,
Год журнала:
2024,
Номер
16(2), С. 217 - 217
Опубликована: Фев. 2, 2024
The
COVID-19
pandemic,
caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
has
presented
an
enormous
challenge
to
health
care
systems
and
medicine.
As
a
result
of
global
research
efforts
aimed
at
preventing
effectively
treating
SARS-CoV-2
infection,
vaccines
with
fundamentally
new
mechanisms
action
some
small-molecule
antiviral
drugs
targeting
key
proteins
in
the
viral
cycle
have
been
developed.
most
effective
drug
approved
date
for
treatment
is
PaxlovidTM,
which
combination
two
protease
inhibitors,
nirmatrelvir
ritonavir.
Nirmatrelvir
reversible
covalent
peptidomimetic
inhibitor
main
(Mpro)
SARS-CoV-2,
enzyme
plays
crucial
role
reproduction.
In
this
combination,
ritonavir
serves
as
pharmacokinetic
enhancer,
it
irreversibly
inhibits
cytochrome
CYP3A4
responsible
rapid
metabolism
nirmatrelvir,
thereby
increasing
half-life
bioavailability
nirmatrelvir.
tutorial
review,
we
summarize
development
pharmaceutical
chemistry
aspects
Paxlovid,
covering
evolution
warhead
design,
synthesis
mechanism
well
its
inhibition
mechanism.
efficacy
Paxlovid
novel
virus
mutants
also
overviewed.
Язык: Английский
Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review
Bioorganic Chemistry,
Год журнала:
2024,
Номер
147, С. 107380 - 107380
Опубликована: Апрель 16, 2024
Язык: Английский
Exploring covalent inhibitors of SARS-CoV-2 main protease: from peptidomimetics to novel scaffolds
Journal of Enzyme Inhibition and Medicinal Chemistry,
Год журнала:
2025,
Номер
40(1)
Опубликована: Фев. 6, 2025
Peptidomimetic
inhibitors
mimic
natural
peptide
substrates,
employing
electrophilic
warheads
to
covalently
interact
with
the
catalytic
Cys145
of
Mpro.
Examples
include
aldehydes,
α-ketoamides,
and
aza-peptides,
discussions
on
their
mechanisms
action,
potency,
structural
insights.
Non-peptidomimetic
utilise
diverse
scaffolds
mechanisms,
achieving
covalent
modification
Язык: Английский
Applications of Molecular Docking Studies in SARS-CoV-2 Targeted Drug Discovery and the Gains Achieved through Molecular Docking
Biomedical engineering,
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 29, 2024
In
this
chapter,
we
delve
into
the
pivotal
role
of
molecular
docking
in
realm
computational
biology
and
chemistry,
focusing
specifically
on
its
application
drug
discovery
targeting
SARS-CoV-2.
Molecular
docking,
a
critical
technique,
has
played
significant
predicting
interactions
bindings
molecules,
particularly
concerning
SARS-CoV-2’s
main
protease
RNA
polymerase.
This
chapter
highlights
synergy
between
virtual
screening,
emphasizing
expedited
identification
evaluation
potential
candidates
against
Through
comprehensive
discussion,
aim
to
provide
nuanced
understanding
rapid
advancements
for
SARS-CoV-2,
accentuating
indispensable
value
tools
methods
contemporary
therapeutic
development.
Язык: Английский
In Silico Development of SARS-CoV-2 Non-covalent Mpro Inhibitors: A Review
Опубликована: Сен. 2, 2024
Coronaviruses
(CoVs)
have
recently
emerged
as
significant
causes
of
respiratory
disease
outbreaks.
The
novel
coronavirus
pneumonia
2019,
known
COVID-19,
are
highly
infectious
and
triggered
by
severe
acute
syndrome
2
(SARS-CoV-2).
Understanding
virus-host
interactions
molecular
targets
in
host
cell
death
signalling
is
crucial
for
treatment
development.
Small
natural
compounds
like
celastrol
curcumin,
acting
proteasome
inhibitors,
can
potentially
modify
NF-κB
treating
SARS-CoV-2
infections.
Various
constituents,
including
alkaloids,
flavonoids,
terpenoids,
diarylheptanoids,
anthraquinones,
inhibit
viral
infection,
progression,
amplification
coronaviruses.
Derived
from
medicinal
herbs,
these
possess
anti-inflammatory
antiviral
properties,
impacting
the
life
cycle,
entry,
replication,
assembly,
release
COVID-19
virions.
This
review
focuses
on
development
small
molecules
non-covalent
inhibitors
targeting
Main
Protease
(Mpro,
also
called
3CLpro)
enzyme
SARS-CoV-2.
It
highlights
design
using
dynamics
(MD)
studies
computational
methods
further
improvements
Mpro
inhibitor
design.
in-silico
approach,
which
pivotal
this
process,
provides
an
accelerated
virtual
avenue
exploring
developing
potential
representing
latest
advancements
drug
Язык: Английский