HIV OctaScanner: A Machine Learning Approach to Unveil Proteolytic Cleavage Dynamics in HIV-1 Protease Substrates
Journal of Chemical Information and Modeling,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 14, 2025
The
rise
of
resistance
to
antiretroviral
drugs
due
mutations
in
human
immunodeficiency
virus-1
(HIV-1)
protease
is
a
major
obstacle
effective
treatment.
These
alter
the
drug-binding
pocket
and
reduce
drug
efficacy
by
disrupting
interactions
with
inhibitors.
Traditional
methods,
such
as
biochemical
assays
structural
biology,
are
crucial
for
studying
enzyme
function
but
time-consuming
labor-intensive.
To
address
these
challenges,
we
developed
HIV
OctaScanner,
machine
learning
algorithm
that
predicts
proteolytic
cleavage
activity
octameric
substrates
at
HIV-1
sites.
uses
Random
Forest
(RF)
classifier
achieves
prediction
accuracy
89%
identification
cleavable
octamers.
This
innovative
approach
facilitates
rapid
screening
potential
protease,
providing
critical
insights
into
guiding
development
more
therapeutic
strategies.
By
improving
substrate
identification,
OctaScanner
has
support
next
generation
treatments.
Language: Английский
Evaluation of the Potency of Repurposed Antiretrovirals in HBV Therapy: A Narrative Investigation of the Traditional Medicine Alternatives
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(4), P. 1523 - 1523
Published: Feb. 11, 2025
Hepatitis
B
is
one
of
the
killer
communicable
diseases,
with
a
global
estimation
1.1
million
deaths
resulting
from
liver
diseases
annually.
The
search
for
HBV
therapeutics
has
resulted
in
repurposing
existing
antiretrovirals
(ARVs)
treatment,
considering
their
shared
common
replication
mechanisms.
This
review
aimed
at
evaluating
potencies
some
repurposed
ARVs
used
analyzing
mechanisms
viral
replications
and
HIV,
investigating
potentials
traditional
medicines
as
an
alternative
treatment
patients.
topical
keywords
drug
repurposing,
repositioning,
antiretrovirals,
hepatitis
HBV,
natural
products,
medicines,
title,
abstract
were
searched
PubMed,
Web
Science,
Google
Scholar.
advanced
included
five
years,
2019-2024.
result
was
filtered
377
to
110
relevant
articles.
evaluation
reveals
that
CD4+
T
cells
are
targeted
by
while
targets
its
associated
(cirrhosis
hepatocellular
carcinoma
(HCC)).
Furthermore,
treatments
available
only
prevent
or
slow
down
progression
cirrhosis,
reduce
HCC
incidence,
can
improve
quality
life
increase
expectancy;
however,
they
not
curative
HBV.
Traditional
medicines/natural
product
extracts
phytochemicals
exert
anti-HBV
effects
through
different
improved
therapeutic
when
combined
properly.
investigation
further
consideration
silico
approach
might
streamline
development
but
also
contribute
deeper
understanding
pathogenesis.
Therefore,
we
recommend
integration
computational
design
methods
medicine
screening
discovering
new
bioactive
candidates.
Language: Английский
From Bench to Bedside: Transforming Cancer Therapy with Protease Inhibitors
Targets,
Journal Year:
2025,
Volume and Issue:
3(1), P. 8 - 8
Published: March 3, 2025
Proteases
play
a
pivotal
role
in
cancer
progression,
facilitating
processes
such
as
extracellular
matrix
degradation,
angiogenesis,
and
metastasis.
Consequently,
protease
inhibitors
have
emerged
promising
therapeutic
agents
oncology.
This
review
provides
comprehensive
overview
of
the
mechanisms
by
which
modulate
biology,
categorizing
their
target
classes,
including
metalloproteinases,
cysteine
proteases,
serine
proteases.
We
discuss
potential
both
synthetic
natural
inhibitors,
highlighting
applications
preclinical
clinical
settings.
Furthermore,
challenges
specificity,
toxicity,
resistance
are
addressed,
alongside
strategies
to
overcome
these
limitations
through
innovative
drug
designs
combination
therapies.
The
future
treatment
lies
precision
medicine,
leveraging
proteomic
profiling
tailor
therapies
individual
tumors.
underscores
importance
ongoing
research
development
novel
approaches
harness
effectively
for
management.
Language: Английский
Research progress on critical viral protease inhibitors for coronaviruses and enteroviruses
Shulei Hu,
No information about this author
Qiuyu Zhong,
No information about this author
Xiong Xie
No information about this author
et al.
Bioorganic & Medicinal Chemistry Letters,
Journal Year:
2025,
Volume and Issue:
unknown, P. 130168 - 130168
Published: March 1, 2025
Language: Английский
Synthesis, screening and validation of cysteine-reactive fragments as chikungunya virus protease inhibitors
Junming He,
No information about this author
Henry Illingworth,
No information about this author
Sven Ullrich
No information about this author
et al.
Bioorganic & Medicinal Chemistry Letters,
Journal Year:
2025,
Volume and Issue:
unknown, P. 130176 - 130176
Published: March 1, 2025
Language: Английский
Potential Benefits of In Silico Methods: A Promising Alternative in Natural Compound’s Drug Discovery and Repurposing for HBV Therapy
Pharmaceuticals,
Journal Year:
2025,
Volume and Issue:
18(3), P. 419 - 419
Published: March 16, 2025
Hepatitis
B
virus
(HBV)
is
an
important
global
public
health
issue.
The
World
Health
Organization
(WHO)
2024
Global
Report
estimated
that
the
prevalence
of
people
living
with
HBV
infection
254
million,
incidence
1.2
million
new
infections
yearly.
Previous
studies
have
shown
natural
compounds
antiviral
inhibition
potentials.
In
silico
methods
such
as
molecular
docking,
virtual
screening,
pharmacophore
modeling,
quantitative
structure–activity
relationship
(QSAR),
and
dynamic
simulations
been
successfully
applied
in
identifying
bioactive
strong
binding
energies
treatment
targets.
COVID-19
pandemic
necessitated
importance
repurposing
already
approved
drugs
using
methods.
This
study
aimed
at
unveiling
benefits
techniques
a
potential
alternative
compounds’
drug
discovery
for
therapy.
Relevant
articles
from
PubMed,
Google
Scholar,
Web
Science
were
retrieved
analyzed.
Furthermore,
this
comprehensively
reviewed
literature
containing
identified
essential
proteins.
Notably,
hesperidin,
quercetin,
kaempferol,
myricetin,
flavonoids
hepatitis
surface
antigen
(HBsAg).
investigation
reveals
offer
understanding
mechanisms
action,
reveal
previously
overlooked
viral
targets
(including
PreS1
Domain
HBsAg
cccDNA
(Covalently
Closed
Circular
DNA)
regulators,
facilitate
creation
specific
inhibitors.
integration
silico,
vitro,
vivo
insights
further
highlight
Moreover,
combination
compounds,
approach,
improves
chances
personalized
precision
medicine
treatment.
Therefore,
we
recommend
strategies
combine
vivo,
approaches
to
effective
drugs.
Language: Английский
Fungi as a Tool to Screen for Microbial Protease Inhibitors
Veena G. Nair,
No information about this author
Vineetha K Unnikrishnan,
No information about this author
Niranjana Sri Sundaramoorthy
No information about this author
et al.
Published: Jan. 1, 2025
Language: Английский
Structure-based discovery of highly bioavailable, covalent, broad-spectrum coronavirus M Pro inhibitors with potent in vivo efficacy
Science Advances,
Journal Year:
2025,
Volume and Issue:
11(17)
Published: April 23, 2025
The
main
protease
(M
Pro
)
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
is
a
validated
drug
target.
Starting
with
lead-like
dihydrouracil
chemotype
identified
in
large-library
docking
campaign,
we
improved
M
inhibition
>1000-fold
by
engaging
additional
subsites
and
using
latent
electrophile
to
engage
Cys
145
.
Advanced
leads
from
this
series
show
pan-coronavirus
antiviral
activity,
low
clearance
mice,
for
AVI-4773
,
rapid
reduction
viral
titers
>1,000,000
after
just
three
doses.
Both
compounds
are
well
distributed
mouse
tissues,
including
brain,
where
concentrations
>1000×
the
90%
effective
concentration
observed
8
hours
oral
dosing
AVI-4516
shows
minimal
major
cytochrome
P450s
human
proteases.
also
exhibits
synergy
RNA-dependent
RNA
polymerase
inhibitor,
molnupiravir,
cellular
infection
models.
Related
analogs
strongly
inhibit
nirmatrelvir-resistant
mutant
virus.
properties
differentiated
existing
clinical
preclinical
inhibitors
will
advance
therapeutic
development
against
emerging
SARS-CoV-2
variants
other
coronaviruses.
Language: Английский
Breaking the Chain: Protease Inhibitors as Game Changers in Respiratory Viruses Management
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(15), P. 8105 - 8105
Published: July 25, 2024
Respiratory
viral
infections
(VRTIs)
rank
among
the
leading
causes
of
global
morbidity
and
mortality,
affecting
millions
individuals
each
year
across
all
age
groups.
These
are
caused
by
various
pathogens,
including
rhinoviruses
(RVs),
adenoviruses
(AdVs),
coronaviruses
(CoVs),
which
particularly
prevalent
during
colder
seasons.
Although
many
VRTIs
self-limiting,
their
frequent
recurrence
potential
for
severe
health
complications
highlight
critical
need
effective
therapeutic
strategies.
Viral
proteases
crucial
maturation
replication
viruses,
making
them
promising
targets.
This
review
explores
pivotal
role
in
lifecycle
respiratory
viruses
development
protease
inhibitors
as
a
strategic
response
to
these
infections.
Recent
advances
antiviral
therapy
have
highlighted
effectiveness
curtailing
spread
severity
diseases,
especially
ongoing
COVID-19
pandemic.
It
also
assesses
current
efforts
aimed
at
identifying
developing
targeting
key
from
major
human
RVs,
AdVs,
(severe
acute
syndrome
coronavirus-2)
SARS-CoV-2.
Despite
recent
identification
SARS-CoV-2,
within
last
five
years,
scientific
community
has
devoted
considerable
time
resources
investigate
existing
drugs
develop
new
virus’s
main
protease.
However,
research
RVs
AdVs
limited.
Therefore,
herein,
it
is
proposed
utilize
this
knowledge
other
tract
or
dual
inhibitors.
Finally,
detailing
mechanisms
action
potentials
inhibitors,
aims
demonstrate
significant
transforming
management
diseases
offer
insights
into
future
directions.
Language: Английский
Global Antiviral Peptide Research: A Bibliometric Analysis from 1951 to 2022
Universitas Scientiarum,
Journal Year:
2024,
Volume and Issue:
29(3), P. 229 - 251
Published: Oct. 10, 2024
Antiviral
peptides
(AVPs)
are
small
molecules
that
inhibit
the
replication
of
viruses
in
living
cells.
AVPs
being
investigated
as
potential
alternatives
to
traditional
antiviral
drugs.
The
development
novel
agents
is
highest
concern
because
some
medications
can
be
ineffective
and
lead
resistant
emergence.
We
conducted
a
bibliometric
study
on
global
distribution
AVP
research
comprehend
trends
patterns
field.
For
this
analysis,
we
retrieved
data
from
Scopus
database
AVP-related
publications
1951
2022,
including
number
publications,
citations,
authors.
Overall,
10,279
papers
were
published,
with
an
annual
average
146
publications.
United
States
released
most
documents,
followed
by
China,
Germany,
Kingdom.
Since
2001,
there
has
been
substantial
increase
AVPs,
prominent
themes
virology,
genetics,
protease
inhibitors,
polypeptide
antimicrobial
agents,
viral
entry.
This
analysis
used
guide
future
Language: Английский