DIONYSUS: a database of protein–carbohydrate interfaces
Nucleic Acids Research,
Год журнала:
2024,
Номер
53(D1), С. D387 - D395
Опубликована: Окт. 22, 2024
Protein-carbohydrate
interactions
govern
a
wide
variety
of
biological
processes
and
play
an
essential
role
in
the
development
different
diseases.
Here,
we
present
DIONYSUS,
first
database
protein-carbohydrate
interfaces
annotated
according
to
structural,
chemical
functional
properties
both
proteins
carbohydrates.
We
provide
exhaustive
information
on
nature
interactions,
binding
site
composition,
function
specific
additional
retrieved
from
existing
databases.
The
user
can
easily
search
using
protein
sequence
structure
or
by
carbohydrate
properties.
Moreover,
for
given
interaction
site,
perform
its
comparison
with
representative
subset
non-covalent
retrieve
potential
specificity.
Therefore,
DIONYSUS
is
source
valuable
deeper
understanding
general
patterns,
annotation
previously
unannotated
such
applications
as
carbohydrate-based
drug
design.
freely
available
at
www.dsimb.inserm.fr/DIONYSUS/.
Язык: Английский
A cost-effective approach for comprehensive analysis of human memory B Cell repertoire: fast isolation of broad neutralizing mAbs to SARS-CoV-2 variants
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 16, 2025
Abstract
The
SARS-CoV-2
pandemic
highlighted
the
urgent
need
for
innovative
methods
to
study
humoral
immune
responses
and
identify
monoclonal
antibodies
(mAbs)
with
diagnostic
therapeutic
potential.
Memory
B
cells
(MBCs),
pivotal
adaptive
immunity,
generate
high-affinity
upon
antigen
re-encounter.
While
single-cell
high-throughput
sequencing
has
revolutionized
antibody
repertoire
studies,
it
critical
limitations:
inability
simultaneously
determine
antigen-binding
specificities
immunoglobulin
gene
sequences,
high
resource
demands
that
limit
accessibility
in
low-resource
settings.
Here,
we
present
a
cost-effective
culture
(SCC)
platform
enabling
comprehensive
analysis
of
human
MBC
repertoires,
including
epitope-specific
responses,
cross-reactivity
mAb
isolation.
Using
convalescent
vaccinated
donor
samples,
optimized
SCCs
NB21
feeder
cells,
R848,
IL-2
stimulation,
achieving
cloning
efficiency
30-fold
enrichment
antigen-specific
MBCs
compared
bulk
cultures.
Among
592
isolated
mAbs,
52.7%
exhibited
specificity
Wuhan
strain
Spike
protein,
27.9%
targeting
receptor-binding
domain
(RBD),
15.4%
N-terminal
(NTD),
56.7%
other
regions,
likely
S2
domain.
Comparative
revealed
distinct
patterns:
40.5%
all
anti-Spike
mAbs
recognized
tested
variants
(Wuhan,
Beta,
Delta,
Gamma
Omicron
BA.2),
while
29.6%
showed
recognition
only
four
variants,
majority
not
BA.2;
56
single
reactive
(14.9%)
were
also
identified.
Notably,
screening
neutralization
assays
performed
directly
supernatants,
eliminating
large-scale
transfection.
Desired
clones
selected
recombinant
production.
SCC
enabled
unbiased
profiling,
revealing
convergent
V-region
rearrangements,
public
V3-30
V3-53/V3-66
consistent
prior
studies.
Two
RBD-targeting
broad
potential
validated
pseudovirus
assays.
This
streamlined
delivers
simultaneous
isolation,
sequencing,
functional
studies
within
seven
days,
empowering
researchers
settings
address
global
health
inequities
enhance
preparedness
future
pandemics.
Язык: Английский
A Structural Voyage Toward the Landscape of Humoral and Cellular Immune Escapes of SARS‐CoV‐2
Immunological Reviews,
Год журнала:
2025,
Номер
330(1)
Опубликована: Фев. 5, 2025
ABSTRACT
The
genome‐based
surveillance
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS‐CoV‐2)
in
the
past
nearly
5
years
since
its
emergence
has
refreshed
our
understanding
virus
evolution,
especially
on
convergent
co‐evolution
with
host.
SARS‐CoV‐2
evolution
been
characterized
by
sets
mutations
that
affect
functional
properties
altering
infectivity,
virulence,
transmissibility,
and
interactions
host
immunity.
This
poses
a
huge
challenge
to
global
prevention
control
measures
based
drug
treatment
vaccine
application.
As
one
key
evasion
strategies
response
immune
profile
human
population,
there
are
overwhelming
amounts
evidence
for
reduced
antibody
neutralization
variants.
Additionally,
data
also
suggest
levels
CD4
+
CD8
T‐cell
responses
against
variants
or
sub‐variants
decrease
populations,
although
non‐negligible
cross‐T‐cell
maintained.
Herein,
from
perspectives
structural
immunology,
we
outline
characteristics
mechanisms
T
cell
SARS‐CoV
variants/sub‐variants.
molecular
bases
impact
escaping
interaction
epitopes
receptors
adaptive
immunity,
is,
major
histocompatibility
complex
(MHC),
receptor
(TCR),
summarized
discussed,
knowledge
which
will
widen
this
pandemic‐threatening
assist
preparedness
Pathogen
X
future.
Язык: Английский
Conformational dynamics of the HIV-1 envelope glycoprotein from CRF01_AE is associated with susceptibility to antibody-dependent cellular cytotoxicity
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 22, 2024
The
HIV-1
envelope
glycoprotein
(Env)
is
expressed
at
the
surface
of
infected
cells
and
as
such
can
be
targeted
by
non-neutralizing
antibodies
(nnAbs)
that
mediate
antibody-dependent
cellular
cytotoxicity
(ADCC).
Previous
single-molecule
Forster
resonance
energy
transfer
(smFRET)
studies
demonstrated
Env
from
clinical
isolates
predominantly
adopt
a
'closed'
conformation
(State
1),
which
resistant
to
nnAbs.
After
interacting
with
receptor
CD4,
conformational
equilibrium
shifts
toward
States
2
3,
exposing
coreceptor
binding
site
(CoRBS)
permitting
targeting
this
site.
We
showed
anti-CoRBS
Abs
enables
engagement
other
nnAbs
target
cluster
A
epitopes
on
Env.
Anti-cluster
stabilize
an
asymmetric
conformation,
State
2A,
have
potent
ADCC
activity.
CRF01_AE
strains
were
suggested
intrinsically
susceptible
mediated
This
may
due
presence
histidine
position
375,
known
shift
towards
more
'open'
conformations.
In
work,
through
adaptation
established
smFRET
imaging
approach,
we
report
dynamics
native,
unliganded
HIV-1CRF01_AE
indicates
frequent
sampling
2A
conformation.
in
striking
contrast
Envs
clades
B,
for
example
HIV-1JR-FL,
do
not
transition
absence
ligands.
These
findings
inform
Env,
are
relevant
structure-based
design
both
synthetic
inhibitors
binding,
enhancers
therapeutic
alternatives.
Язык: Английский
Phytonutrient Formulation Using Gum Arabic and Adansonia Digitata Pulp: Lessons for Boosting the Human Immune System - Part 1
Phytomedicine Plus,
Год журнала:
2024,
Номер
unknown, С. 100663 - 100663
Опубликована: Окт. 1, 2024
Язык: Английский
Multi-step shapeshifting of SARS-CoV-2 Omicron spikes during fusion
Structure,
Год журнала:
2024,
Номер
32(11), С. 1850 - 1851
Опубликована: Ноя. 1, 2024
Язык: Английский
Computational Insights into Acrylamide Fragment Inhibition of SARS-CoV-2 Main Protease
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(11), С. 12847 - 12865
Опубликована: Ноя. 12, 2024
The
pathogen
of
COVID-19,
SARS-CoV-2,
has
caused
a
severe
global
health
crisis.
So
far,
while
COVID-19
been
suppressed,
the
continuous
evolution
SARS-CoV-2
variants
reduced
effectiveness
vaccines
such
as
mRNA-1273
and
drugs
Remdesivir.
To
uphold
prior
to
potential
coronavirus
outbreaks,
it
is
necessary
explore
underlying
mechanisms
between
biomolecules
nanodrugs.
experimental
study
reported
that
acrylamide
fragments
covalently
attached
Cys145,
main
protease
enzyme
(Mpro)
occupied
substrate
binding
pocket,
thereby
disrupting
dimerization.
However,
mechanism
linking
them
unclear.
purpose
this
work
complement
validate
results,
well
facilitate
novel
antiviral
drugs.
Based
on
our
studies,
we
identified
two
constructed
corresponding
protein-ligand
complex
models.
Subsequently,
performed
molecular
dynamics
(MD)
simulations
unveil
crucial
interaction
these
nanodrugs
Mpro.
This
approach
allowed
capture
various
conformations
both
monomeric
dimeric
Mpro,
revealing
significant
conformational
dissociation
catalytic
helix
domains,
which
indicates
presence
allosteric
targets.
Notably,
Compound
5
destabilizes
Mpro
dimerization
acts
an
effective
inhibitor
by
specifically
targeting
active
site,
resulting
in
enhanced
inhibitory
effects.
Consequently,
can
modulate
Mpro’s
equilibrium
among
extended
monomeric,
compact,
forms,
shedding
light
small
molecules
inhibitors
against
coronaviruses.
Overall,
research
contributes
broader
understanding
drug
development
fragment-based
approaches
covalent
therapeutics.
Язык: Английский
Cellular sialoglycans are differentially required for endosomal and cell-surface entry of SARS-CoV-2 in lung cell lines
PLoS Pathogens,
Год журнала:
2024,
Номер
20(12), С. e1012365 - e1012365
Опубликована: Дек. 3, 2024
Cell
entry
of
severe
acute
respiratory
coronavirus-2
(SARS-CoV-2)
and
other
CoVs
can
occur
via
two
distinct
routes.
Following
receptor
binding
by
the
spike
glycoprotein,
membrane
fusion
be
triggered
cleavage
either
at
cell
surface
in
a
transmembrane
serine
protease
2
(TMPRSS2)-dependent
manner
or
within
endosomes
cathepsin-dependent
manner.
Cellular
sialoglycans
have
been
proposed
to
aid
CoV
attachment
entry,
although
their
functional
contributions
each
pathway
are
unknown.
In
this
study,
we
used
genetic
enzymatic
approaches
deplete
sialic
acid
from
surfaces
compared
requirement
for
during
endosomal
cell-surface
using
lentiviral
particles
pseudotyped
with
proteins
different
sarbecoviruses.
We
show
that
SARS-CoV-1,
WIV1-CoV
WIV16-CoV,
like
SARS-CoV-2
omicron
variant,
depends
on
cathepsins
requires
cellular
entry.
Ancestral
delta
variant
use
but
only
require
cells
lacking
TMPRSS2.
Binding
protein
did
not
acid,
nor
was
required
TMRPSS2-expressing
cells.
These
findings
suggest
strictly
attachment,
fusion,
rather
promote
endocytic
related
contrast,
MERS-CoV
pseudoparticles
authentic
HCoV-OC43
affected
TMPRSS2
expression,
consistent
described
role
merbecovirus
embecovirus
attachment.
Overall,
these
clarify
mediate
endosomal,
cell-surface,
Язык: Английский
Development of a two-component recombinant vaccine for COVID-19
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 20, 2024
Though
COVID-19
as
a
public
health
emergency
of
international
concern
(PHEIC)
was
declared
to
be
ended
by
the
WHO,
it
continues
pose
significant
threat
human
society.
Vaccination
remains
one
most
effective
methods
for
preventing
COVID-19.
While
antigenic
regions
are
found
in
receptor
binding
domain
(RBD),
N-terminal
(NTD)
S
protein
is
another
crucial
region
inducing
neutralizing
antibodies
(nAbs)
against
Язык: Английский