ACS Chemical Biology,
Год журнала:
2023,
Номер
18(5), С. 1180 - 1191
Опубликована: Апрель 27, 2023
SARS-CoV-2
viruses
engage
ACE2
as
a
functional
receptor
with
their
spike
protein.
The
S1
domain
of
the
protein
contains
C-terminal
binding
(RBD)
and
an
N-terminal
(NTD).
NTD
other
coronaviruses
includes
glycan
cleft.
However,
for
NTD,
protein–glycan
was
only
observed
weakly
sialic
acids
highly
sensitive
methods.
Amino
acid
changes
in
variants
concern
(VoC)
show
antigenic
pressure,
which
can
be
indication
NTD-mediated
binding.
Trimeric
proteins
SARS-CoV-2,
alpha,
beta,
delta,
omicron
did
not
reveal
capability.
Unexpectedly,
beta
subvariant
strain
(501Y.V2-1)
to
Vero
E6
cells
sialidase
pretreatment.
Glycan
microarray
analyses
identified
putative
9-O-acetylated
ligand,
confirmed
by
catch-and-release
ESI-MS,
STD-NMR
analyses,
graphene-based
electrochemical
sensor.
variant
attained
enhanced
modality
specificity
toward
structures,
suggesting
dual-receptor
functionality
domain,
quickly
selected
against.
These
results
indicate
that
probe
additional
evolutionary
space,
allowing
receptors
on
surface
target
cells.
Science Immunology,
Год журнала:
2022,
Номер
7(74)
Опубликована: Май 10, 2022
Neutralizing
antibodies
that
recognize
the
SARS-CoV-2
spike
glycoprotein
are
principal
host
defense
against
viral
invasion.
Variants
of
bear
mutations
allow
escape
from
neutralization
by
many
human
antibodies,
especially
those
in
widely
distributed
(“public”)
classes.
Identifying
neutralize
these
variants
concern
and
determining
their
prevalence
important
goals
for
understanding
immune
protection.
To
determine
Delta
Omicron
BA.1
variant
specificity
B
cell
repertoires
established
an
initial
Wuhan
strain
infection,
we
measured
potencies
73
unbiased
survey
early
memory
response.
Antibodies
recognizing
each
three
previously
defined
epitopic
regions
on
receptor
binding
domain
(RBD)
varied
potency
variant-escape
resistance.
The
ACE2
surface
(“RBD-2”)
harbored
sites
neutralizing
with
highest
but
greatest
sensitivity
to
escape;
two
other
RBD
(“RBD-1”
“RBD-3”)
bound
more
modest
greater
breadth.
structures
several
Fab:spike
complexes
neutralized
all
five
tested,
including
one
Fab
RBD-1,
-2,
-3
clusters,
illustrated
determinants
broad
showed
can
have
specificities
avoid
driven
public
antibodies.
structure
RBD-2
binding,
neutralizer
shows
why
it
retains
activity
BA.1,
unlike
most
others
same
class.
Our
results
correlate
real-world
data
vaccine
efficacy,
which
indicate
mitigation
disease
caused
BA.1.
Emerging Microbes & Infections,
Год журнала:
2022,
Номер
11(1), С. 2412 - 2422
Опубликована: Сен. 15, 2022
The
devastating
economic
and
public
health
consequences
caused
by
the
COVID-19
pandemic
have
prompted
outstanding
efforts
from
scientific
community
pharmaceutical
companies
to
develop
antibody-based
therapeutics
against
SARS-CoV-2.
Those
are
encouraging
fruitful.
An
unprecedentedly
large
number
of
monoclonal
antibodies
(mAbs)
targeting
a
spectrum
epitopes
on
spike
protein
has
been
developed
in
last
two
years.
development
structural
biology,
especially
cryo-EM
technology,
provides
insights
into
molecular
neutralizing
mechanisms
those
mAbs.
Moreover,
essential
protecting
host
infection.
Therefore,
understanding
antibody
mechanism
is
critical
for
optimizing
effective
developing
next-generation
pan-coronavirus
vaccines.
This
review
summarizes
latest
SARS-CoV-2
at
levels.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июль 19, 2022
Abstract
Recently
emerged
SARS-CoV-2
Omicron
subvariant,
BA.2.75,
displayed
a
local
growth
advantage
over
BA.2.38,
BA.2.76
and
BA.5
in
India.
The
underlying
mechanism
of
BA.2.75’s
enhanced
infectivity,
especially
compared
to
BA.5,
remains
unclear.
Here,
we
show
that
BA.2.75
exhibits
substantially
higher
ACE2-binding
affinity
than
BA.5.
Also,
spike
shows
decreased
thermostability
increased
“up”
RBD
conformation
acidic
conditions,
suggesting
low-pH-endosomal
cell-entry
pathway
utilization.
is
less
humoral
immune
evasive
BA.4/BA.5
BA.1/BA.2
breakthrough-infection
convalescents;
however,
heavier
neutralization
evasion
Delta
convalescents.
Importantly,
plasma
from
breakthrough
infection
exhibit
significantly
weaker
against
mainly
due
distinct
NTD-targeting
antibody
escaping
pattern
BA.4/BA.5.
Additionally,
Evusheld
Bebtelovimab
remain
effective
Sotrovimab
recovered
RBD-binding
affinity.
Together,
our
results
suggest
may
prevail
after
the
global
wave,
its
receptor-binding
capability
could
allow
further
incorporation
immune-evasive
mutations.
ACS Chemical Biology,
Год журнала:
2023,
Номер
18(5), С. 1180 - 1191
Опубликована: Апрель 27, 2023
SARS-CoV-2
viruses
engage
ACE2
as
a
functional
receptor
with
their
spike
protein.
The
S1
domain
of
the
protein
contains
C-terminal
binding
(RBD)
and
an
N-terminal
(NTD).
NTD
other
coronaviruses
includes
glycan
cleft.
However,
for
NTD,
protein–glycan
was
only
observed
weakly
sialic
acids
highly
sensitive
methods.
Amino
acid
changes
in
variants
concern
(VoC)
show
antigenic
pressure,
which
can
be
indication
NTD-mediated
binding.
Trimeric
proteins
SARS-CoV-2,
alpha,
beta,
delta,
omicron
did
not
reveal
capability.
Unexpectedly,
beta
subvariant
strain
(501Y.V2-1)
to
Vero
E6
cells
sialidase
pretreatment.
Glycan
microarray
analyses
identified
putative
9-O-acetylated
ligand,
confirmed
by
catch-and-release
ESI-MS,
STD-NMR
analyses,
graphene-based
electrochemical
sensor.
variant
attained
enhanced
modality
specificity
toward
structures,
suggesting
dual-receptor
functionality
domain,
quickly
selected
against.
These
results
indicate
that
probe
additional
evolutionary
space,
allowing
receptors
on
surface
target
cells.
