Proceedings of the National Academy of Sciences,
Journal Year:
2023,
Volume and Issue:
120(5)
Published: Jan. 24, 2023
SARS-CoV-2
spike
requires
proteolytic
processing
for
viral
entry.
A
polybasic
furin-cleavage
site
(FCS)
in
spike,
and
evolution
toward
an
optimized
FCS
by
dominant
variants
of
concern
(VOCs),
are
linked
to
enhanced
infectivity
transmission.
Here
we
show
interferon-inducible
restriction
factors
Guanylate-binding
proteins
(GBP)
2
5
interfere
with
furin-mediated
cleavage
inhibit
the
early-lineage
isolates
Wuhan-Hu-1
VIC.
By
contrast,
VOCs
Alpha
Delta
escape
GBP2/5
that
map
substitution
D614G
present
these
VOCs.
Despite
inhibition
cleavage,
viruses
remained
sensitive
plasma
membrane
IFITM1,
but
not
endosomal
IFITM2
3,
consistent
a
preference
TMPRSS2-dependent
Strikingly,
find
Omicron
is
unique
among
VOCs,
being
GBP2/5,
also
2,
3.
Using
chimeric
mutants,
phenotype
S1
domain
determines
Omicron's
sensitivity
whereas
S2'
its
IFITM2/3
preferential
use
TMPRSS2-independent
We
propose
has
allowed
from
GBP
factors,
selective
pressures
on
changes
mediate
antibody
escape,
altered
tropism,
have
come
at
expense
increased
innate
immune
target
virus
Cell Reports,
Journal Year:
2022,
Volume and Issue:
39(7), P. 110829 - 110829
Published: April 29, 2022
We
report
that
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
Delta
spike
mutation
P681R
plays
a
key
role
in
the
Alpha-to-Delta
variant
replacement
during
disease
2019
(COVID-19)
pandemic.
SARS-CoV-2
efficiently
outcompetes
Alpha
human
lung
epithelial
cells
and
primary
airway
tissues.
The
is
located
at
furin
cleavage
site
separates
1
(S1)
S2
subunits.
Reverting
to
wild-type
P681
significantly
reduces
replication
of
level
lower
than
variant.
Mechanistically,
enhances
full-length
S1
S2,
which
could
improve
cell-surface-mediated
virus
entry.
In
contrast,
also
has
same
amino
acid
(P681H),
but
reduced
compared
with
spike.
Our
results
suggest
as
enhancing
Delta-variant
via
increased
S1/S2
cleavage.
Journal of Virology,
Journal Year:
2022,
Volume and Issue:
96(6)
Published: Feb. 28, 2022
Emerging
strains
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
the
causative
agent
disease
2019
(COVID-19)
pandemic,
that
show
increased
transmission
fitness
and/or
immune
evasion
are
classified
as
"variants
concern"
(VOCs).
Recently,
a
SARS-CoV-2
variant
first
identified
in
November
2021
South
Africa
has
been
recognized
fifth
VOC,
termed
"Omicron."
What
makes
this
VOC
so
alarming
is
high
number
changes,
especially
viral
Spike
protein,
and
accumulating
evidence
for
efficiency
escape
from
neutralizing
antibodies.
In
an
amazingly
short
time,
Omicron
outcompeted
previously
dominating
Delta
VOC.
However,
it
seems
overall
less
pathogenic
than
other
VOCs.
Here,
we
provide
overview
mutations
genome
resulting
changes
proteins
compared
to
discuss
their
potential
functional
consequences.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: July 19, 2022
Recently,
a
large
number
of
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
variants
continuously
emerged
and
posed
major
threat
to
global
public
health.
Among
them,
particularly,
Omicron
variant
(B.1.1.529),
first
identified
in
November
2021,
carried
numerous
mutations
its
spike
protein
(S),
then
quickly
spread
around
the
world.
Currently,
has
expanded
into
more
than
one
hundred
sublineages,
such
as
BA.1,
BA.2,
BA.2.12.1,
BA.4
BA.5,
which
have
already
become
globally
dominant
variants.
Different
from
other
concern
(VOCs)
SARS-CoV-2,
sublineages
exhibit
increased
transmissibility
immune
escape
neutralizing
antibodies
generated
through
previous
infection
or
vaccination,
caused
re-infections
breakthrough
infections.
In
this
prospective,
we
focused
on
origin,
virological
features,
evasion
intervention
will
benefit
development
next-generation
vaccines
therapeutics,
including
pan-sarbecovirus
universal
anti-CoV
combat
currently
circulating
future
emerging
well
SARS-CoV-2
Cell Host & Microbe,
Journal Year:
2022,
Volume and Issue:
30(8), P. 1093 - 1102.e3
Published: April 25, 2022
Recent
reports
of
SARS-CoV-2
Omicron
variant
sub-lineages,
BA.1,
BA.1.1,
and
BA.2,
have
reignited
concern
over
potential
escape
from
vaccine-
infection-induced
immunity.
We
examine
the
sensitivity
these
sub-lineages
other
major
variants
to
neutralizing
antibodies
mRNA-vaccinated
boosted
individuals,
as
well
recovered
COVID-19
patients,
including
those
infected
with
Omicron.
find
that
all
especially
BA.1
exhibit
substantial
immune
is
largely
overcome
by
mRNA
vaccine
booster
doses.
While
BA.1.1
escapes
almost
completely
neutralization
early-pandemic
patient
sera
a
lesser
extent
Delta-infected
sensitive
Omicron-infected
sera.
Critically,
are
comparably
neutralized
These
results
highlight
importance
doses
for
protection
against
provide
insight
into
immunity
natural
infection
sub-lineages.
Molecular Biology and Evolution,
Journal Year:
2022,
Volume and Issue:
39(4)
Published: March 16, 2022
Among
the
30
nonsynonymous
nucleotide
substitutions
in
Omicron
S-gene
are
13
that
have
only
rarely
been
seen
other
SARS-CoV-2
sequences.
These
mutations
cluster
within
three
functionally
important
regions
of
at
sites
will
likely
impact
(1)
interactions
between
subunits
Spike
trimer
and
predisposition
to
shift
from
down
up
configurations,
(2)
with
ACE2
receptors,
(3)
priming
for
membrane
fusion.
We
show
here
that,
based
on
both
rarity
these
intrapatient
sequencing
reads
patterns
selection
codon
where
occur
related
sarbecoviruses,
prior
emergence
would
predicted
decrease
fitness
any
virus
which
they
occurred.
further
propose
each
clusters
therefore
cooperatively
interact
mitigate
their
individual
costs,
and,
combination
mutations,
adaptively
alter
function
Spike.
Given
evident
epidemic
growth
advantages
overall
previously
known
lineages,
it
is
crucial
determine
how
such
complex
highly
adaptive
mutation
constellations
were
assembled
S-gene,
why,
despite
unprecedented
global
genomic
surveillance
efforts,
early
stages
this
assembly
process
went
completely
undetected.
