Decoding Allosteric Effects of Missense Variations in Drug Metabolism: Afrocentric CYP3A4 Alleles Explored
Rehema Mukami Mwaniki,
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Wayde Veldman,
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Allan Sanyanga
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et al.
Journal of Molecular Biology,
Journal Year:
2025,
Volume and Issue:
unknown, P. 169160 - 169160
Published: April 1, 2025
Language: Английский
Transfer Learning Towards Predicting Viral Missense Mutations: A Case Study on SARS-CoV-2
S. Govender,
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Emily L Morgan,
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Rabelani Ramahala
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et al.
Computational and Structural Biotechnology Journal,
Journal Year:
2025,
Volume and Issue:
27, P. 1686 - 1692
Published: Jan. 1, 2025
Understanding
viral
evolution
and
predicting
future
mutations
are
crucial
for
overcoming
drug
resistance
developing
long-lasting
treatments.
Previously,
we
established
machine
learning
(ML)
models
using
dynamic
residue
network
(DRN)
metric
data
leveraging
a
vast
amount
of
existing
mutation
from
the
SARS-CoV-2
main
protease
(Mpro).
Here,
sought
to
assess
generalizability
robustness
current
across
other
proteins.
To
achieve
this,
first
time,
employed
transfer
(TL)
approach,
allowing
us
determine
extent
which
Mpro
trained
could
be
applied
The
TL
results
were
highly
promising,
with
artificial
neural
(ANN)
random
forest
(RF)
correlation
coefficients
closely
matching
those
NSP10,
NSP16,
PLpro.
ANN
|R|
value
was
0.564,
while
PLpro
had
values
0.533,
0.527,
0.464,
respectively.
Similarly,
RF
0.673,
compared
0.457,
0.460,
0.437
PLpro,
Interestingly,
did
not
observe
strong
spike
(S)
protein
monomer
its
domains.
low
p-values
that
associated
show
linear
correlations
between
predicted
actual
frequencies
statistically
significant.
This
indicates
may
generalize
well
structurally
related
proteins
DRN-derived
ML
model
Mpro.
Overall,
aim
develop
universal
missense
in
proteins,
this
study
lays
foundation
goal.
Language: Английский
SARS-CoV-2 damages cardiomyocyte mitochondria and implicates long COVID-associated cardiovascular manifestations
Wenliang Che,
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Shuai Guo,
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Yanqun Wang
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et al.
Journal of Advanced Research,
Journal Year:
2025,
Volume and Issue:
unknown
Published: May 1, 2025
With
the
COVID-19
pandemic
becoming
endemic,
vigilance
for
Long
COVID-related
cardiovascular
issues
remains
essential,
though
their
specific
pathophysiology
is
largely
unexplored.
Our
study
investigates
persistent
symptoms
observed
in
individuals
long
after
contracting
SARS-CoV-2,
a
condition
commonly
referred
to
as
"Long
COVID",
which
has
significantly
affected
millions
globally.
We
meticulously
describe
outcomes
five
patients,
encompassing
range
of
severe
conditions
such
sudden
cardiac
death
during
exercise,
coronary
atherosclerotic
heart
disease,
palpitation,
chest
tightness,
and
acute
myocarditis.
All
patients
were
diagnosed
with
myocarditis,
confirmed
through
endomyocardial
biopsy
histochemical
staining,
identified
inflammatory
cell
infiltration
tissue.
Crucially,
electron
microscopy
revealed
widespread
mitochondrial
vacuolations
presence
myofilament
degradation
within
cardiomyocytes
these
patients.
These
findings
mirrored
SARS-CoV-2-infected
mice,
suggesting
potential
underlying
cellular
mechanism
effects
associated
COVID.
demonstrate
profound
impact
SARS-CoV-2
on
integrity,
shedding
light
implications
Language: Английский