Journal of Carbohydrate Chemistry,
Journal Year:
2023,
Volume and Issue:
42(4-6), P. 197 - 215
Published: July 24, 2023
Human
coronavirus
OC43
(HCoV-OC43)
causes
severe
respiratory
tract
illness
in
humans.
In
the
present
study,
we
carried
out
100
ns
molecular
dynamics
(MD)
simulations
to
investigate
conformational
of
HCoV-OC43
spike
(S)
glycoprotein
complexes
with
sialic
acid
(SIA)
analogs.
The
binding
affinity
between
S
and
SIA
analogs
is
analyzed
using
NAMD
MM-PBSA
free
energy
calculation.
It
concluded
from
results
MM/PBSA
that
order
specificity
toward
9-O-Ac-Sia
>
Neu5Gc
zanamivir
Neu5Ac2en.
Vaccines,
Journal Year:
2024,
Volume and Issue:
12(11), P. 1236 - 1236
Published: Oct. 30, 2024
New
SARS-CoV-2
lineages
continue
to
evolve
and
may
exhibit
new
characteristics
regarding
host
cell
entry
efficiency
potential
for
antibody
evasion.
Here,
employing
pseudotyped
particles,
we
compared
the
efficiency,
ACE2
receptor
usage,
sensitivity
antibody-mediated
neutralization
of
four
emerging
lineages,
KP.2,
KP.2.3,
KP.3,
LB.1.
The
XBB.1.5
JN.1
served
as
controls.
Our
findings
reveal
that
LB.1
enter
cells
efficiently
in
an
ACE2-dependent
manner,
KP.3
is
more
adept
at
entering
Calu-3
lung
than
JN.1.
However,
variants
differed
their
capacity
employ
orthologues
from
animal
species
entry,
suggesting
differences
interactions.
Moreover,
demonstrate
only
two
out
seven
therapeutic
monoclonal
(mAbs)
preclinical
development
retain
robust
neutralizing
activity
against
sublineages
tested,
while
three
mAbs
displayed
strongly
reduced
lacked
any
tested.
Furthermore,
our
results
show
evade
by
antibodies
induced
infection
or
vaccination
with
greater
JN.1,
particularly
individuals
without
hybrid
immunity.
This
study
indicates
differ
interactions
suggest
evasion
drove
emergence
these
variants.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 24, 2024
Coronaviruses
recognize
a
wide
array
of
protein
and
glycan
receptors
using
the
S1
subunit
spike
(S)
glycoprotein.
The
contains
two
functional
domains:
N-terminal
(S1-NTD)
C-terminal
(S1-CTD).
S1-NTD
SARS-CoV-2,
MERS-CoV,
HCoV-HKU1
possess
an
evolutionarily
conserved
binding
cleft
that
facilitates
weak
interactions
with
sialic
acids
on
cell
surfaces.
employs
9-
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(31), P. 21700 - 21709
Published: July 25, 2024
Interactions
between
glycan-binding
proteins
(GBPs)
and
glycosphingolipids
(GSLs)
present
in
cell
membranes
are
implicated
a
wide
range
of
biological
processes.
However,
studying
GSL
binding
is
hindered
by
the
paucity
purified
GSLs
weak
affinities
typical
monovalent
GBP–GSL
interactions.
Native
mass
spectrometry
(nMS)
performed
using
soluble
model
promising
approach
for
discovery
GBP
ligands,
but
detection
interactions
remains
challenging.
The
work
introduces
MEmbrane
ANchor-assisted
nMS
(MEAN-nMS)
low-affinity
complexes.
assay
utilizes
membrane
anchor,
produced
covalent
cross-linking
lipid
membrane,
to
localize
on
surface
promote
binding.
Ligands
identified
intact
complexes
or
catch-and-release
(CaR)
strategy,
wherein
released
from
upon
collisional
activation
detected
(MEAN-CaR-nMS).
To
establish
reliability,
library
gangliosides
incorporated
into
nanodiscs
was
screened
against
human
immune
lectins,
results
compared
with
corresponding
ganglioside
oligosaccharides.
Without
analysis
yielded
predominantly
false
negatives.
In
contrast,
all
ligands
were
MEAN-(CaR)-nMS,
no
positives.
highlight
potential
MEAN-CaR-nMS
ligand
discovery,
natural
viral
uncover
elusive
ligands.
Finally,
nMS-based
directly
cells
demonstrated.
This
breakthrough
paves
way
shotgun
glycomics
screening
cells.
ACS Infectious Diseases,
Journal Year:
2024,
Volume and Issue:
10(11), P. 3880 - 3890
Published: Oct. 12, 2024
Coronaviruses
(CoVs)
recognize
a
wide
array
of
protein
and
glycan
receptors
by
using
the
S1
subunit
spike
(S)
glycoprotein.
The
contains
two
functional
domains:
N-terminal
domain
(S1-NTD)
C-terminal
(S1-CTD).
S1-NTD
SARS-CoV-2,
MERS-CoV,
HCoV-HKU1
possesses
an
evolutionarily
conserved
binding
cleft
that
facilitates
weak
interactions
with
sialic
acids
on
cell
surfaces.
employs
9-O-acetylated
α2-8-linked
disialylated
structures
for
initial
binding,
followed
TMPRSS2
receptor
virus–cell
fusion.
Here,
we
demonstrate
NTD
has
broader
repertoire
than
previously
recognized.
We
presented
Fc
chimeras
nanoparticle
system
to
mimic
densely
decorated
surface
HCoV-HKU1.
These
proteins
were
expressed
HEK293S
GnTI–
cells,
generating
species
carrying
Man-5
structures,
often
observed
near
site
CoVs.
This
multivalent
presentation
high
mannose-containing
revealed
much
profile
compared
its
fully
glycosylated
counterpart.
Using
microarrays,
α2-3-linked
sialylated
LacNAc
are
also
bound,
comparable
OC43
NTD,
suggesting
glycan-binding
modality.
Further
characterization
specificity
indicated
promiscuous
toward
sialoglycans,
independent
core
(glycolipids,
N-
or
O-glycans).
may
employ
additional
sialoglycan
trigger
conformational
changes
in
glycoprotein
expose
S1-CTD
proteinaceous
binding.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(24), P. 13649 - 13649
Published: Dec. 20, 2024
The
COVID-19
pandemic,
caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
has
resulted
in
hundreds
of
millions
infections
and
deaths
globally.
Although
vaccination
campaigns
are
mitigating
the
emerging
viral
variants
continue
to
pose
challenges.
spike
(S)
protein
SARS-CoV-2
plays
a
critical
role
entry
binding
angiotensin-converting
enzyme
(ACE2)
receptor,
making
both
proteins
essential
targets
for
therapeutic
vaccine
development.
glycosylation
these
influences
their
structure
function.
This
underscores
need
detailed
site-specific
glycoproteomic
analysis.
In
this
study,
we
characterized
N-
or
O-glycosylation
profiles
recombinant
receptor-binding
domain
(RBD)
ACE2
expressed
from
Expi293F
cells,
as
well
S2
subunit
plant
(N.
benthamiana)
cells.
Using
high-resolution
Orbitrap
Eclipse
Tribrid
mass
spectrometer
equipped
with
Ultimate
3000
RSLCnano
I-GPA
(Integrated
GlycoProteome
Analyzer)
developed
previous
148
28
O-glycopeptides
RBD,
71
N-glycopeptides
subunit,
139
were
characterized.
addition,
report
post-translational
modifications
(PTMs)
glycan,
including
mannose-6-phosphate
(M6P)
GlcNAc-1-phosphate-6-O-mannose
N-glycan
RBD
ACE2,
O-acetylation
O-glycan
identified
first
time
proteins.
relative
abundance
distribution
according
glycosites
glycan
types
analyzed
quantified
O
(only
RBD)-glycopeptides
S2,
using
I-GPA.
Asn331
Asn1098
Asn103
majorly
N-glycosylated,
dominant
glycan-type
was
complex
high-mannose
S2.
These
findings
will
provide
valuable
insights
into
patterns
that
influence
function
immunogenicity
offer
new
perspectives
development
vaccines
antibody-based
therapies
against
COVID-19.
RSC Chemical Biology,
Journal Year:
2023,
Volume and Issue:
5(2), P. 148 - 157
Published: Nov. 23, 2023
Fast
and
reliable
virus
diagnostics
is
key
to
prevent
the
spread
of
viruses
in
populations.
A
hallmark
presence
multivalent
surface
proteins,
a
property
that
can
be
harnessed
control
conformational
switching
sensor
proteins.
Here,
we
introduce
new
platform
(dark-LUX)
for
detection
viral
proteins
consisting
general
bioluminescent
framework
post-translationally
functionalized
with
separately
expressed
binding
domains.
The
relies
on
(1)
plug-and-play
bioconjugation
different
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 22, 2023
Abstract
Fast
and
reliable
virus
diagnostics
is
key
to
prevent
the
spread
of
viruses
in
populations.
A
hallmark
presence
multivalent
surface
proteins,
a
property
that
can
be
harnessed
control
conformational
switching
sensor
proteins.
Here,
we
introduce
new
platform
(dark-LUX)
for
detection
viral
proteins
consisting
general
bioluminescent
framework
post-translationally
functionalized
with
separately
expressed
binding
domains.
The
relies
on
1)
plug-and-play
bioconjugation
different
via
SpyTag/SpyCatcher
technology
create
branched
protein
structures,
2)
an
optimized
turn-on
switch
based
complementation
split-luciferase
NanoBiT
upon
target
3)
straightforward
exploration
linker
space.
influenza
(IAV)
hemagglutinin
(HA)
neuraminidase
(NA)
were
used
as
relevant
targets
establish
proof
principle
optimize
parameters
such
properties,
choice
domains
optimal
combination
competing
components
SmBiT
DarkBiT.
allows
rapid
conjugation
exchange
various
including
scFvs,
nanobodies
de
novo
designed
binders
variety
targets,
construction
heterobivalent
head
stem
region
hemagglutinin.
modularity
thus
optimization
scaffold
properties
existing
well
suited
quickly
adapt
effectively
detect
newly
evolving
epitopes.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 23, 2023
Abstract
Enveloped
viruses
carry
one
or
multiple
proteins
with
receptor
binding
functionalities.
Functional
receptors
can
either
be
glycans,
proteinaceous
both,
recombinant
protein
approaches
are
instrumental
to
gain
more
insight
into
these
properties.
Visualizing
and
measuring
normally
entails
antibody
detection
direct
labelling,
whereas
fluorescent
fusions
attractive
tools
in
molecular
biology.
Here
we
report
a
suite
of
different
fusions,
both
N-
and/or
C-terminal,
for
influenza
A
virus
hemagglutinins
SARS-CoV-2
spike
RBD.
The
contained
total
three
six
barrels
were
applied
directly
cells
determine
Journal of Carbohydrate Chemistry,
Journal Year:
2023,
Volume and Issue:
42(4-6), P. 197 - 215
Published: July 24, 2023
Human
coronavirus
OC43
(HCoV-OC43)
causes
severe
respiratory
tract
illness
in
humans.
In
the
present
study,
we
carried
out
100
ns
molecular
dynamics
(MD)
simulations
to
investigate
conformational
of
HCoV-OC43
spike
(S)
glycoprotein
complexes
with
sialic
acid
(SIA)
analogs.
The
binding
affinity
between
S
and
SIA
analogs
is
analyzed
using
NAMD
MM-PBSA
free
energy
calculation.
It
concluded
from
results
MM/PBSA
that
order
specificity
toward
9-O-Ac-Sia
>
Neu5Gc
zanamivir
Neu5Ac2en.