bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Dec. 13, 2023
SUMMARY
SARS-CoV-2,
like
many
viruses,
generates
syncytia.
Using
SARS-CoV-2
and
S
(S)
expressing
recombinant
vesicular
stomatitis
influenza
A
we
show
that
S-mediated
syncytia
formation
provides
resistance
to
interferons
in
cultured
cells,
human
small
airway-derived
air-liquid
interface
cultures
hACE2
transgenic
mice.
Amino
acid
substitutions
modulate
fusogenicity
Delta-
Omicron-derived
have
parallel
effects
on
viral
interferon
resistance.
Syncytia
also
decreases
antibody
virus
neutralization
activity
cells.
These
findings
explain
the
continued
selection
of
fusogenic
variants
during
evolution
humans
and,
more
generally,
viruses
despite
adverse
replication
absence
innate
or
adaptive
immune
pressure.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Feb. 13, 2024
A
recombinant
lineage
of
the
SARS-CoV-2
Omicron
variant,
named
XBB,
appeared
in
late
2022
and
evolved
descendants
that
successively
swept
local
global
populations.
XBB
members
were
noted
for
their
improved
immune
evasion
transmissibility.
Here,
we
determine
cryo-EM
structures
XBB.1.5,
XBB.1.16,
EG.5
EG.5.1
spike
(S)
ectodomains
to
reveal
reinforced
3-RBD-down
receptor
inaccessible
closed
states
mediated
by
interprotomer
binding
domain
(RBD)
interactions
previously
observed
BA.1
BA.2.
Improved
XBB.1.5
XBB.1.16
RBD
stability
compensated
loss
caused
early
mutations,
while
F456L
substitution
reduced
stability.
S1
subunit
mutations
had
long-range
impacts
on
conformation
epitope
presentation
S2
subunit.
Our
results
continued
S
protein
evolution
via
simultaneous
optimization
multiple
parameters
including
stability,
evasion,
dramatic
effects
relatively
few
residue
substitutions
altering
conformational
landscape.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 6, 2024
Abstract
The
measurement
of
neutralizing
immune
responses
to
viral
infection
is
essential,
given
the
heterogeneity
human
immunity
and
emergence
new
virus
strains.
However,
antibody
(nAb)
assays
often
require
high-level
biosafety
containment,
sophisticated
instrumentation,
long
detection
times.
Here,
as
a
proof-of-principle,
we
designed
nanoparticle-supported,
rapid,
electronic
(NasRED)
assay
assess
potency
monoclonal
antibodies
(mAbs)
against
SARS-CoV-2.
gold
nanoparticles
(AuNPs)
coated
with
angiotensin-converting
enzyme
2
(ACE2)
protein
nAb
reporters
were
mixed
mAbs
be
tested,
well
streptavidin-conjugated
multivalent
spike
(S)
or
their
receptor
binding
domains
(RBD).
High-affinity
ACE2-competitive
nAbs
alter
S
(or
RBD)-to-ACE2
level
modulate
AuNP
cluster
formation
precipitation.
amount
free-floating
quantified
by
semiconductor-based
readout
system
that
measures
AuNPs’
optical
extinction,
producing
signals
can
differentiate
SARS-CoV-2
variants
(Wuhan-Hu-1,
Gamma,
Omicron).
modular
design
nature,
short
time
(less
than
30
minutes),
portable
inexpensive
make
this
NasRED-nAb
applicable
measuring
vaccine
potency,
infection,
efficacy
antibody-based
therapies.
Viruses,
Journal Year:
2024,
Volume and Issue:
16(6), P. 912 - 912
Published: June 4, 2024
The
Omicron
variant
and
its
sub-lineages
are
the
only
current
circulating
SARS-CoV-2
viruses
worldwide.
In
this
study,
conformational
stability
of
isolated
Receptor
Binding
Domain
(RBD)
Omicron’s
spike
protein
is
examined
in
detail.
parent
lineage
has
over
ten
mutations
ACE2
binding
region
RBD
that
specifically
associated
with
β
hairpin
loop
domain.
It
demonstrated
through
biophysical
molecular
computations
domain
significantly
increase
intra-protein
interaction
energies
intra-loop
loop–RBD
interactions.
energy
increases
include
formation
new
hydrogen
bonds
help
stabilize
critical
region.
Our
results
also
agree
recent
experiments
on
core
barrel
domain,
outside
demonstrate
overall
RBD.
further
shown
here
dynamic
simulations
unbound
state
remains
closely
aligned
bound
configuration,
which
was
not
observed
for
wild-type
Overall,
these
studies
increased
configuration
raise
a
number
questions
whether
could
be
positive
selection
feature
viral
mutational
changes.
Research Square (Research Square),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Jan. 9, 2024
Abstract
The
Omicron
variant
and
its
sub
lineages
are
the
only
current
circulating
SARS-CoV-2
viruses
world-wide.
In
this
study,
conformational
stability
of
isolated
Receptor
Binding
Domain
(RBD)
virus’s
spike
protein,
which
has
been
used
for
highly
successful
vaccines
(Ref.
12),
is
examined
in
detail.
Omicron’s
RBD
over
Wild-type
(WT)
strain
shown
to
be
greatly
increased
traceable
just
a
few
mutations:
K417N,
S373P,
E484A.
mutation
S373P,which
represent
significant
beta
strand
enhancement
within
receptor
binding
domain,
previously
identified
through
atomic
force
microscopy
19)
as
critical
biomechanical
variant.
Here
it
demonstrated
that
these
stabilizing
mutations
significantly
increase
internal
energy
RBD,
specifically
associated
with
β
hairpin
loop
domain
interactions
(intra-loop
loop-RBD
interactions).
These
increases
traced
formation
new
hydrogens
bonds
between
non-mutated
residues
brought
closer
together
more
stable
structure.
Furthermore,
enhanced
WT
results
configurational
alignment
bound
state
conformation
partner
(human)
Angiotensin
Converting
Enzyme
II.
nearly
identical
across
variants.
This
suggests
dynamic,
energetic
analysis
protein
unbound
conformations
may
potentially
provide
general
“road
map”
site
directed
mutational
proteins
antigens
vaccines.
Frontiers in Neurology,
Journal Year:
2024,
Volume and Issue:
15
Published: July 26, 2024
Background
Fangcang
shelter
hospitals
are
quarantine
facilities
offering
primary
medical
treatment
for
mild
and
asymptomatic
SARS-CoV-2
cases.
Little
is
known
about
the
age-specific
prevalence
of
insomnia
among
patients
in
hospitals,
particularly
older
age
groups.
Methods
This
cross-sectional
study
was
conducted
three
largest
during
lockdown
period,
from
March
to
May
2022,
Shanghai.
The
patients’
demographic
information
recorded.
Insomnia
defined
according
prescriptions
zolpidem
estazolam.
overall
risk
factors
were
investigated
through
regression
models.
Results
A
total
2,39,448
included
this
(59.09%
male,
median
42,
73.41%
asymptomatic),
with
being
3.1%.
varied
across
different
groups
(<18
years:
0.23%,
18–64
2.64%,
≥65
10.36%).
vaccine,
regardless
number
doses,
significantly
associated
a
decreased
group
aged
years.
Three
doses
vaccine
reduced
An
extra
day
hospital
increased
by
approximately
10%
all
Mild
symptoms
higher
<65
years
old,
while
male
residing
surrounding
area
negatively
adults.
Conclusion
observed
that
high-risk
population
developing
hospitals.
vaccination
might
decrease
adults,
especially
adult,
which
indicates
benefits
reducing
infected
patients.
