bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 31, 2023
Knowledge
of
the
fitness
effects
mutations
to
SARS-CoV-2
can
inform
assessment
new
variants,
design
therapeutics
resistant
escape,
and
understanding
functions
viral
proteins.
However,
experimentally
measuring
is
challenging:
we
lack
tractable
lab
assays
for
many
proteins,
comprehensive
deep
mutational
scanning
has
been
applied
only
two
Here
develop
an
approach
that
leverages
millions
publicly
available
sequences
estimate
mutations.
We
first
calculate
how
independent
occurrences
each
mutation
are
expected
be
observed
along
phylogeny
in
absence
selection.
then
compare
these
observations
actual
effect
mutation.
These
estimates
correlate
well
with
measurements.
For
most
genes,
synonymous
nearly
neutral,
stop-codon
deleterious,
amino-acid
have
a
range
effects.
some
accessory
proteins
under
little
no
provide
interactive
visualizations
all
(https://jbloomlab.github.io/SARS2-mut-fitness/).
The
framework
describe
applicable
any
virus
which
number
sufficiently
large
neutral
observed.
PLoS Pathogens,
Год журнала:
2023,
Номер
19(12), С. e1011868 - e1011868
Опубликована: Дек. 20, 2023
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
XBB
lineages
have
achieved
dominance
worldwide
and
keep
on
evolving.
Convergent
evolution
of
the
receptor-binding
domain
(RBD)
L455F
F456L
is
observed,
resulting
in
variants
with
substantial
growth
advantages,
such
as
EG.5,
FL.1.5.1,
XBB.1.5.70,
HK.3.
Here,
we
show
that
neutralizing
antibody
(NAb)
evasion
drives
convergent
F456L,
while
epistatic
shift
caused
by
enables
subsequent
convergence
through
ACE2
binding
enhancement
further
immune
evasion.
evade
RBD-targeting
Class
1
public
NAbs,
reducing
neutralization
efficacy
breakthrough
infection
(BTI)
reinfection
convalescent
plasma.
Importantly,
single
substitution
significantly
dampens
receptor
binding;
however,
combination
forms
an
adjacent
residue
flipping,
which
leads
to
enhanced
NAbs
resistance
affinity.
The
perturbed
mode
exceptional
NAb
evasion,
revealed
structural
analyses.
Our
results
indicate
flexibility
contributed
epistasis
cannot
be
underestimated,
potential
SARS-CoV-2
RBD
remains
high.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Янв. 3, 2023
Abstract
SARS-CoV-2
recombinant
subvariant
XBB.1.5
is
growing
rapidly
in
the
United
States,
carrying
an
additional
Ser486Pro
substitution
compared
to
XBB.1
and
outcompeting
BQ.1.1
other
XBB
sublineages.
The
underlying
mechanism
for
such
high
transmissibility
remains
unclear.
Here
we
show
that
exhibits
a
substantially
higher
hACE2-binding
affinity
XBB/XBB.1.
Convalescent
plasma
samples
from
BA.1,
BA.5,
BF.7
breakthrough
infection
are
significantly
evaded
by
both
XBB.1.5,
with
displaying
slightly
weaker
immune
evasion
capability
than
XBB.1.
Evusheld
Bebtelovimab
could
not
neutralize
XBB.1/XBB.1.5,
while
Sotrovimab
weakly
reactive
notably,
SA55
still
highly
effective.
fact
showed
comparable
antibody
but
distinct
suggests
enhanced
receptor-binding
would
indeed
lead
growth
advantages.
strong
hACE2
binding
of
also
enable
its
tolerance
further
escape
mutations,
which
should
be
closely
monitored.
Cellular and Molecular Immunology,
Год журнала:
2023,
Номер
20(4), С. 419 - 422
Опубликована: Март 3, 2023
Since
late
2022,
the
share
of
infections
caused
by
SARS-CoV-2
lineage
XBB.1.5has
gradually
increased
in
United
States,
resulting
XBB.1.5becoming
dominating
States
and
a
similar
trend
is
likely
to
soon
take
place
also
European
countries.However,
information
on
virological
properties
XBB.1.5
scarce.Here,
we
conducted
an
initial
assessment
XBB.1.5lineage.The
XBB
possesses
extraordinarily
high
capacity
for
antibody
evasion
due
its
unique
set
S
protein
mutations
[1][2][3][4].However,
this
trait
may
have
come
at
cost
moderately
reduced
host
cell
entry
efficiency
as
suggested
recent
vitro
data
[1,5],
which
explain
why
sublineages
only
accounted
small
proportion
total
several
countries
(except
India)
so
far
(Fig.
1a).Recently,
has
changed
where
sublineage
since
XBB.1.5now
represents
1a).Moreover,
although
being
presently
detected
low
frequencies
only,
increase
XBB.1.5-relatedinfections
observed
1a).The
XBB.1.5S
differs
one
mutation
(S486P)
from
parental
XBB.1
lineage,
located
receptor-binding
domain
(RBD)
1b).Thus,
it
affect
transmissibility
modulating
efficiency,
alter
sensitivity
antibody-mediated
neutralization.Here,
performed
XBB.1.5lineage
neutralization,
using
protein-bearing
pseudovirus
particles
(pp),
are
suitable
model
system
analysis
neutralization
[6].Particles
pseudotyped
with
ancestral
B.1
(B.1
pp
)
or
Omicron
BA.4/BA.5
(identical
amino
acid
level,
BA.4-5
),
BQ.1.1
(BQ.1.1
(XBB.1
were
used
comparison.First,
compared
line
tropism
different
pseudoviruses.As
expected,
displayed
augmented
most
lines
tested
exception
Cell,
Год журнала:
2023,
Номер
186(23), С. 5151 - 5164.e13
Опубликована: Окт. 23, 2023
The
large-scale
evolution
of
the
SARS-CoV-2
virus
has
been
marked
by
rapid
turnover
genetic
clades.
New
variants
show
intrinsic
changes,
notably
increased
transmissibility,
and
antigenic
changes
that
reduce
cross-immunity
induced
previous
infections
or
vaccinations.
How
this
functional
variation
shapes
global
remained
unclear.
Here,
we
establish
a
predictive
fitness
model
for
integrates
selection.
is
informed
tracking
time-resolved
sequence
data,
epidemiological
records,
cross-neutralization
data
viral
variants.
Our
inference
shows
immune
pressure,
including
contributions
vaccinations
infections,
become
dominant
force
driving
recent
SARS-CoV-2.
can
serve
continued
surveillance
in
two
ways.
First,
it
successfully
predicts
short-term
circulating
strains
flags
emerging
likely
to
displace
previously
predominant
variant.
Second,
profiles
successful
escape
prior
their
emergence.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Май 12, 2023
Understanding
the
longitudinal
dynamics
of
antibody
immunity
following
heterologous
SAR-CoV-2
breakthrough
infection
will
inform
development
next-generation
vaccines.
Here,
we
track
SARS-CoV-2
receptor
binding
domain
(RBD)-specific
responses
up
to
six
months
Omicron
BA.1
in
mRNA-vaccinated
individuals.
Cross-reactive
serum
neutralizing
and
memory
B
cell
(MBC)
decline
by
two-
four-fold
through
study
period.
Breakthrough
elicits
minimal
de
novo
BA.1-specific
but
drives
affinity
maturation
pre-existing
cross-reactive
MBCs
toward
BA.1,
which
translates
into
enhanced
breadth
activity
across
other
variants.
Public
clones
dominate
response
at
both
early
late
time
points
breakthough
infection,
their
escape
mutation
profiles
predict
newly
emergent
sublineages,
suggesting
that
convergent
continue
shape
evolution.
While
is
limited
our
relatively
small
cohort
size,
these
results
suggest
variant
exposure
evolution
memory,
supporting
continued
variant-based
Protein & Cell,
Год журнала:
2024,
Номер
15(6), С. 403 - 418
Опубликована: Март 4, 2024
Intensive
selection
pressure
constrains
the
evolutionary
trajectory
of
SARS-CoV-2
genomes
and
results
in
various
novel
variants
with
distinct
mutation
profiles.
Point
mutations,
particularly
those
within
receptor
binding
domain
(RBD)
spike
(S)
protein,
lead
to
functional
alteration
both
engagement
monoclonal
antibody
(mAb)
recognition.
Here,
we
review
data
RBD
point
mutations
possessed
by
major
discuss
their
individual
effects
on
ACE2
affinity
immune
evasion.
Many
single
amino
acid
substitutions
epitopes
crucial
for
evasion
capacity
may
conversely
weaken
affinity.
However,
this
weakened
effect
could
be
largely
compensated
specific
epistatic
such
as
N501Y,
thus
maintaining
overall
protein
all
variants.
The
predominant
direction
evolution
lies
neither
promoting
nor
evading
mAb
neutralization
but
a
delicate
balance
between
these
two
dimensions.
Together,
interprets
how
efficiently
resist
meanwhile
is
maintained,
emphasizing
significance
comprehensive
assessment
mutations.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Апрель 22, 2024
Abstract
The
continuous
evolution
of
SARS-CoV-2,
particularly
the
emergence
BA.2.86/JN.1
lineage
replacing
XBB
lineages,
necessitates
re-evaluation
current
vaccine
compositions.
Here,
we
provide
a
comprehensive
analysis
humoral
immune
response
to
and
JN.1
human
exposures,
emphasizing
need
for
JN.1-lineage-based
boosters.
We
demonstrate
antigenic
distinctiveness
lineages
in
SARS-CoV-2-naive
individuals
but
not
those
with
prior
vaccinations
or
infections,
infection
elicits
superior
plasma
neutralization
titers
against
its
subvariants.
highlight
strong
evasion
receptor
binding
capability
KP.3,
supporting
foreseeable
prevalence.
Extensive
BCR
repertoire,
isolating
∼2000
RBD-specific
monoclonal
antibodies
(mAbs)
their
targeting
epitopes
characterized
by
deep
mutational
scanning
(DMS),
underscores
systematic
superiority
JN.1-elicited
memory
B
cells
(MBCs).
Notably,
Class
1
IGHV3-53/3-66-derived
neutralizing
(NAbs)
contribute
majorly
within
wildtype
(WT)-reactive
NAbs
JN.1.
However,
KP.2
KP.3
evade
substantial
subset
them,
even
induced
JN.1,
advocating
booster
updates
optimized
enrichment.
JN.1-induced
Omicron-specific
also
high
potency
across
all
Omicron
lineages.
Escape
hotspots
these
have
mainly
been
mutated
RBD,
resulting
higher
barrier
escape,
considering
probable
recovery
previously
escaped
NAbs.
Additionally,
prevalence
broadly
reactive
IGHV3-53/3-66-
encoding
MBCs,
competing
suggests
inhibitory
role
on
de
novo
activation
naive
cells,
potentially
explaining
heavy
imprinting
mRNA-vaccinated
individuals.
These
findings
delineate
evolving
antibody
shift
from
importance
developing
lineage,
especially
KP.3-based
boosters,
enhance
immunity
future
SARS-CoV-2
variants.