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.
Chemical Biology & Drug Design,
Journal Year:
2023,
Volume and Issue:
103(1)
Published: Oct. 24, 2023
Abstract
Carbapenem‐resistant
Klebsiella
pneumoniae
(CRKP)
infections
continue
to
impose
high
morbidity
threats
hospitalized
patients
worldwide,
limiting
therapeutic
options
last‐resort
antibiotics
like
colistin.
However,
the
dynamic
genomic
landscape
of
colistin‐resistant
K.
(COLR‐Kp)
invoked
ardent
exploration
underlying
molecular
signatures
for
propositions/designs.
We
unveiled
structural
impact
widespread
and
emerging
PmrB
mutations
involved
in
colistin
resistance
(COLR)
.
In
present
study,
clinical
isolates
expressed
variable
susceptibilities
(>0.5
μg/mL
resistant
≤0.25
susceptible)
despite
such
as
T157P,
G207D
T246A.
The
protein
sequences
extracted
from
in‐house
sequenced
genomes
were
used
model
mutant
proteins
analyze
alterations.
contrasted
based
on
dynamics
simulation
trajectories,
free‐energy
landscapes
flexibility
profiles.
altered
backbone
flexibilities
can
be
an
essential
factor
selection
by
COLR
provide
clues
deal
with
mutants.
Furthermore,
having
druggability
confidence
(>0.99),
was
explored
a
potential
target
1396
virtually
screened
FDA‐approved
drug
candidates.
Among
top‐10
compounds
(scores
>70),
amphotericin
B
found
candidate
affinity
(Binding
energy
<−8
kcal/mol)
stable
interactions
(RMSF
<0.7
Å)
against
druggable
pockets,
mutations,
which
encourages
future
adjunct
research
COLR‐Kp.
Research Square (Research Square),
Journal Year:
2021,
Volume and Issue:
unknown
Published: Aug. 10, 2021
Abstract
Metallo-β-lactamases
(MBLs)
producing
bacteria
especially
the
ones
with
New
Delhi
metallo-beta-lactamase-1
(NDM-1)
and
its
variants
can
potentially
hydrolyse
all
major
β-lactam
antibiotics,
ultimately
escalating
anti-microbial
resistance
world-wide.
There
is
a
dearth
of
approved
inhibitors
to
combat
NDM
other
MBLs
bacteria.
Hence
we
focussed
find
novel
inhibitor(s)
in-silico
which
suppress
activity
NDM/MBLs.
A
total
2400
compounds
were
virtually
screened
identify
promising
carboxylic
acid-containing
compound
(CID-53986787)
analogous
antagonist
Captopril.
Our
lead
bind
adjacent
active
site
zinc
ions
(Zn1
Zn2)
in
highly
resistant
variants.
CID-53986787
possesses
~
5–8%
higher
binding
affinity
than
Captopril,
exhibiting
molecular
interactions
crucial
residues
that
destabilize
hydrolytic
NDM.
was
evaluated
ascertain
safe
pharmacological/toxicity
profile.
Molecular
dynamics
simulation
studies
further
elucidated
stable
interaction
target
protein
(NDM-1).
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.
