The Journal of Physical Chemistry B,
Год журнала:
2024,
Номер
128(14), С. 3340 - 3349
Опубликована: Апрель 2, 2024
The
emergence
of
the
variant
concern
Omicron
(B.1.1.529)
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
exacerbates
COVID-19
pandemic
due
to
its
high
contagious
ability.
Studies
have
shown
that
binds
human
ACE2
more
strongly
than
wild
type.
prevalence
in
new
cases
promotes
novel
lineages
with
improved
receptor
binding
affinity
and
immune
evasion.
To
shed
light
on
this
open
problem,
work,
we
investigated
free
energy
domain
BA.2,
BA.2.3.20,
BA.3,
BA4/BA5,
BA.2.75,
BA.2.75.2,
BA.4.6,
XBB.1,
XBB.1.5,
BJ.1,
BN.1,
BQ.1.1,
CH.1.1
using
all-atom
molecular
dynamics
simulation
mechanics
Poisson–Boltzmann
surface
area
method.
results
show
these
increased
compared
BA.1
lineage,
BA.2.75
BA.2.75.2
subvariants
bind
others.
However,
general,
affinities
do
not
differ
significantly
from
each
other.
electrostatic
force
dominates
over
van
der
Waals
interaction
between
cells.
Based
our
results,
argue
viral
evolution
does
further
improve
SARS-CoV-2
for
but
may
increase
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Окт. 20, 2022
Abstract
Continued
evolution
of
SARS-CoV-2
has
led
to
the
emergence
several
new
Omicron
subvariants,
including
BQ.1,
BQ.
1.1,
BA.4.6,
BF.7
and
BA.2.75.2.
Here
we
examine
neutralization
resistance
these
as
well
their
ancestral
BA.4/5,
BA.2.75
D614G
variants,
against
sera
from
3-dose
vaccinated
health
care
workers,
hospitalized
BA.1-wave
patients,
BA.5-wave
patients.
We
found
enhanced
in
all
especially
BQ.1
BQ.1.1
subvariants
driven
by
a
key
N460K
mutation,
lesser
extent,
R346T
K444T
mutations,
BA.2.75.2
subvariant
largely
its
F486S
mutation.
The
also
exhibited
fusogenicity
S
processing
dictated
Interestingly,
saw
an
enhancement
mutation
reduction
D1199N
processing,
resulting
minimal
overall
change.
Molecular
modelling
revealed
mechanisms
receptor-binding
non-receptor
binding
monoclonal
antibody-mediated
immune
evasion
R346T,
K444T,
mutations.
Altogether,
findings
shed
light
on
concerning
newly
emerging
subvariants.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 21, 2023
Although
the
SARS-CoV-2
Omicron
variant
(BA.1)
spread
rapidly
across
world
and
effectively
evaded
immune
responses,
its
viral
fitness
in
cell
animal
models
was
reduced.
The
precise
nature
of
this
attenuation
remains
unknown
as
generating
replication-competent
genomes
is
challenging
because
length
genome
(~30
kb).
Here,
we
present
a
plasmid-based
assembly
rescue
strategy
(pGLUE)
that
constructs
complete
infectious
viruses
or
noninfectious
subgenomic
replicons
single
ligation
reaction
with
>80%
efficiency.
Fully
sequenced
stocks
can
be
generated
1
3
weeks,
respectively.
By
testing
series
naturally
occurring
well
Delta-Omicron
chimeric
replicons,
show
nonstructural
protein
6
harbors
critical
attenuating
mutations,
which
dampen
RNA
replication
reduce
lipid
droplet
consumption.
Thus,
pGLUE
overcomes
remaining
barriers
to
broadly
study
reveals
deficits
function
underlying
attenuation.
Viruses,
Год журнала:
2022,
Номер
14(9), С. 1999 - 1999
Опубликована: Сен. 9, 2022
Evusheld®
(tixagevimab
+
cilgavimab;
AZD7442)
was
the
first
anti-Spike
monoclonal
antibody
(mAb)
cocktail
designed
not
only
for
treatment
but
also
with
pre-exposure
prophylaxis
in
mind.
The
immunoglobulins
were
engineered
prolonged
half-life
by
modifying
Fc
fragment,
thus
creating
a
long-acting
(LAAB).
We
review
here
preclinical
development,
baseline
and
treatment-emergent
resistance,
clinical
efficacy
from
registration
trials,
real-world
post-marketing
evidence.
combination
initially
approved
at
time
of
SARS-CoV-2
Delta
VOC
wave
based
on
trial
conducted
unvaccinated
subjects
when
Alpha
dominant.
Another
proved
as
early
patients
led
to
authorization
BA.4/5
wave.
Tixagevimab
ineffective
against
any
Omicron
sublineage,
so
cilgavimab
has
far
been
ingredient
which
made
difference.
Antibody
monotherapy
high
risk
selecting
immune
escape
variants
immunocompromised
viral
loads,
nowadays
represent
main
therapeutic
indication
therapies.
Among
sublineages,
BA.1,
recovered
BA.2
BA.2.12.1,
lost
again
BA.4/BA.5
BA.2.75.
Our
analysis
indicated
that
used
during
phase
without
robust
data
this
variant
suggested
several
regulatory
decisions
regarding
its
use
lacked
consistency.
There
is
an
urgent
need
new
randomized
controlled
trials
vaccinated,
subjects,
using
COVID-19
convalescent
plasma
control
arm.
Nature Immunology,
Год журнала:
2023,
Номер
24(4), С. 690 - 699
Опубликована: Март 13, 2023
Abstract
The
omicron
variants
of
SARS-CoV-2
have
substantial
ability
to
escape
infection-
and
vaccine-elicited
antibody
immunity.
Here,
we
investigated
the
extent
such
in
nine
convalescent
patients
infected
with
wild-type
during
first
wave
pandemic.
Among
total
476
monoclonal
antibodies
(mAbs)
isolated
from
peripheral
memory
B
cells,
identified
seven
mAbs
broad
neutralizing
activity
all
tested,
including
various
subvariants.
Biochemical
structural
analysis
indicated
majority
these
bound
receptor-binding
domain,
mimicked
receptor
ACE2
were
able
accommodate
or
inadvertently
improve
recognition
substitutions.
Passive
delivery
representative
protected
K18-hACE2
mice
infection
beta
SARS-CoV-2.
A
deeper
understanding
how
cells
that
produce
could
be
selectively
boosted
recalled
can
augment
immunity
against
variants.
Current Opinion in Virology,
Год журнала:
2023,
Номер
62, С. 101349 - 101349
Опубликована: Авг. 28, 2023
SARS
coronavirus
2
(SARS-CoV-2),
the
causative
agent
of
COVID-19,
emerged
in
China
December
2019.
Vaccines
developed
were
very
effective
initially,
however,
virus
has
shown
remarkable
evolution
with
multiple
variants
spreading
globally
over
last
three
years.
Nowadays,
newly
emerging
Omicron
lineages
are
gaining
substitutions
at
a
fast
rate,
resulting
escape
from
neutralization
by
antibodies
that
target
Spike
protein.
Tools
to
map
impact
on
further
antigenic
SARS-CoV-2,
such
as
cartography,
may
be
helpful
update
SARS-CoV-2
vaccines.
In
this
review,
we
focus
highlighting
protein
individually
and
combination
immune
escape.
