Medical and Veterinary Entomology,
Journal Year:
2022,
Volume and Issue:
37(2), P. 213 - 218
Published: Nov. 15, 2022
Louse-borne
relapsing
fever
(LBRF)
with
high
untreated
mortality
caused
by
spirochete
Borrelia
recurrentis
is
predominantly
endemic
to
Sub-Saharan
Africa
and
has
re-emerged
in
parts
of
Eastern
Europe,
Asia
Latin
America
due
population
migrations.
Despite
subtractive
evolution
lice-borne
pathogenic
spp.
from
tick-borne
species,
there
been
no
comprehensive
report
on
conservation
protein
targets
across
tick
nor
exploration
phytocompounds
that
are
toxic
against
lice.
From
the
19
available
whole
genomes
including
B.
recurrentis,
burgdorferi,
hermsii,
parkeri
miyamotoi,
seven
drug
(>80%
domain
identity)
viz.
30
S
ribosomal
subunit
proteins
(RSP)
S3,
S7,
S8,
S14,
S19,
penicillin-binding
protein-2
50
RSP
L16
were
deciphered
through
multiple
sequence
alignments.
Twelve
(hydroxy-tyrosol,
baicalein,
cis-2-decanoic
acid,
morin,
oenin,
rosemarinic
kaempferol,
piceatannol,
rottlerin,
luteolin,
fisetin
monolaurin)
previously
explored
Lyme
disease
burgdorferi
when
targeted
LBRF-causing
revealed
multi-target
affinity
(2%-20%
higher
than
conventional
antibiotics)
molecular
docking.
However,
based
binding
all
target
proteins,
stable
coarse-grained
dynamics
(fluctuations
<1
Å)
safe
pharmacological
profile,
luteolin
was
prioritized.
The
study
encourages
experimental
evaluation
potent
similar
protocols
for
investigating
other
emerging
vector-borne
diseases.
Frontiers in Cellular and Infection Microbiology,
Journal Year:
2021,
Volume and Issue:
11
Published: Sept. 13, 2021
Background
The
incidence
of
hypervirulent
(hv)
carbapenem-resistant
(CR)
Klebsiella
pneumoniae
(Kp)
is
increasing
globally
among
various
clones
and
also
responsible
for
nosocomial
infections.
CR-hvKp
formed
by
the
uptake
a
virulence
plasmid
endemic
high-risk
or
plasmids
carrying
antimicrobial
resistance
genes
virulent
clones.
Here,
we
describe
from
India
belonging
to
that
have
acquired
are
phenotypically
unidentified
due
lack
hypermucoviscosity.
Methods
Twenty-seven
CRKp
isolates
were
identified
possess
rmpA2
whole-genome
sequencing;
determinants
characterized.
By
in
silico
protein
modeling
(and
validation),
backbone
stability
analysis,
coarse
dynamics
study,
fitness
RmpA,
RmpA2,
aerobactin-associated
proteins-IucA
IutA,
determined
establish
reliable
marker
clinical
identification
CR-hvKp.
Results
belonged
multidrug-resistant
(MDR)
such
as
CG11,
CG43,
ST15,
ST231
carried
OXA-232
predominant
carbapenemase
followed
NDM.
IncHI1B
replicon
type
frameshifted
truncated
rmpA
.
This
resulted
hypermucoviscous
phenotype.
However,
functional
aerobactin
was
expressed
all
In
analysis
portrayed
IucA
IutA
more
stable
than
classical
RmpA.
Furthermore,
had
lower
conformational
fluctuations
domains
non-functional
which
increases
cost
latter
its
maintenance
expression
Hence,
RmpA
RmpA2
likely
be
lost
owing
increased
while
coding
essential
factors.
Conclusion
Increasing
convergence
AMR
observed
K.
globally,
warrants
need
markers
identifying
presence
highlights
significance
molecular
negative
string
test
challenges
phenotypic
screening
faster
this
pathotype.
can
potentially
counteracted
projecting
stable,
constitutively
expressed,
rapidly
evolving
Frontiers in Microbiology,
Journal Year:
2022,
Volume and Issue:
12
Published: Feb. 3, 2022
The
principal
causative
agent
of
acute
bacterial
meningitis
(ABM)
in
children
and
the
elderly
is
Streptococcus
pneumoniae,
with
a
widespread
increase
penicillin
resistance.
Resistance
due
to
non-synonymous
single-nucleotide
polymorphisms
(nsSNPs)
that
alter
penicillin-binding
proteins
(PBPs),
targets
for
all
β-lactam
drugs.
Hence,
resistance
against
one
antibiotic
may
positively
select
another.
Since
meropenem
an
alternative
cefotaxime
meningeal
infections,
we
aim
identify
whether
nsSNPs
PBPs
causing
can
decrease
pneumococcal
susceptibility
meropenem.
Comparison
between
cefotaxime-resistant
Indian
(n
=
33)
global
isolates
28)
revealed
PBP1A
alone
elevated
minimal
inhibitory
concentrations
(MICs)
0.12
μg/ml,
both
PBP2X
2B
combined
increases
MIC
≥
0.25
μg/ml.
Molecular
docking
confirmed
PBP
drug
binding
affinity
nsSNPs,
thereby
increasing
inhibition
potential
values,
leading
Structural
dynamics
thermodynamic
stability
pattern
as
result
mutations
further
depicted
accumulation
certain
functional
domains
reduced
without
majorly
affecting
overall
proteins.
Restricting
usage
promoting
combination
therapy
antibiotics
having
non-PBPs
treat
non-susceptible
S.
pneumoniae
prevent
selection
Viruses,
Journal Year:
2022,
Volume and Issue:
14(11), P. 2504 - 2504
Published: Nov. 12, 2022
Outbreaks
of
monkeypox
virus
infections
have
imposed
major
health
concerns
worldwide,
with
high
morbidity
threats
to
children
and
immunocompromised
adults.
Although
repurposed
drugs
vaccines
are
being
used
curb
the
disease,
evolving
traits
virus,
exhibiting
considerable
genetic
dynamicity,
challenge
limits
a
targeted
treatment.
A
pan-genome-based
reverse
vaccinology
approach
can
provide
fast
efficient
solutions
resolve
persistent
inconveniences
in
experimental
vaccine
design
during
an
outbreak-exigency.
The
encompassed
screening
available
whole
genomes
(n
=
910)
identify
viral
targets.
From
102
screened
targets,
proteins
L5L,
A28,
L5
were
finalized
based
on
their
location,
solubility,
antigenicity.
potential
T-cell
B-cell
epitopes
extracted
from
using
immunoinformatics
tools
algorithms.
Multiple
constructs
designed
by
combining
epitopes.
Based
immunological
properties,
chemical
stability,
structural
quality,
novel
multi-epitopic
construct,
V4,
was
finalized.
Flexible-docking
coarse-dynamics
simulation
portrayed
that
V4
had
binding
affinity
towards
human
HLA-proteins
(binding
energy
<
−15.0
kcal/mol)
low
conformational
fluctuations
(<1
Å).
Thus,
construct
(V4)
may
act
as
induce
immunity
against
monkeypox,
which
encourages
validation
similar
approaches
emerging
infections.
Computational and Structural Biotechnology Journal,
Journal Year:
2022,
Volume and Issue:
20, P. 4271 - 4287
Published: Jan. 1, 2022
Parkinson's
disease
(PD)
has
been
designated
as
one
of
the
priority
neurodegenerative
disorders
worldwide.
Although
diagnostic
biomarkers
have
identified,
early
onset
detection
and
targeted
therapy
are
still
limited.
An
integrated
systems
structural
biology
approach
were
adopted
to
identify
therapeutic
targets
for
PD.
From
a
set
49
PD
associated
genes,
densely
connected
interactome
was
constructed.
Based
on
centrality
indices,
degree
interaction
functional
enrichments,
LRRK2,
PARK2,
PARK7,
PINK1
SNCA
identified
hub-genes.
PARK2
(Parkin)
finalized
potent
theranostic
candidate
marker
due
its
strong
association
(score
>0.99)
with
α-synuclein
(SNCA),
which
directly
regulates
progression.
Besides,
modeling
validation
Parkin
structure,
an
extensive
virtual-screening
revealed
small
(commercially
available)
inhibitors
against
Parkin.
Molecule-258
(ZINC5022267)
selected
based
pharmacokinetic
profiles,
Density
Functional
Theory
(DFT)
energy
calculations
(ΔE=6.93eV)
high
binding
affinity
(Binding
energy=-6.57±0.1kcal/mol;
Inhibition
constant=15.35µM)
Molecular
dynamics
simulation
protein-inhibitor
complexes
further
strengthened
propositions
stable
trajectories
(low
fluctuations),
hydrogen
bonding
patterns
interactive
energies
(>0kJ/mol).
Our
study
encourages
experimental
validations
novel
drug
prevent
auto-inhibition
mediated
ubiquitination
in
