RAB5 is a host dependency factor for the generation of SARS-CoV-2 replication organelles
mBio,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 1, 2025
ABSTRACT
Severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
remains
a
threat
due
to
the
emergence
of
variants
with
increased
transmissibility
and
enhanced
escape
from
immune
responses.
Like
other
coronaviruses
before,
SARS-CoV-2
likely
emerged
after
its
transmission
bats.
The
successful
propagation
in
humans
might
have
been
facilitated
by
usurping
evolutionarily
conserved
cellular
factors
execute
crucial
steps
life
cycle,
such
as
generation
replication
organelles—membrane
structures
where
assemble
their
replication-transcription
complex.
In
this
study,
we
found
that
RAB5,
which
is
highly
across
mammals,
critical
host
dependency
factor
for
genome.
Our
results
also
suggest
uses
RAB5
+
membranes
build
organelles
aid
COPB1,
component
COP-I
complex,
virus
protein
NSP6
participates
process.
Hence,
targeting
represents
promising
approach
interfere
RNA
synthesis
halt
propagation.
IMPORTANCE
sought
identify
severe
organelles:
membranous
builds
order
support
transcription
We
uncovered
an
important
organelles,
viral
target
replication.
Language: Английский
Rapid-response RNA-fluorescence in situ hybridization (FISH) assay platform for coronavirus antiviral high-throughput screening
SLAS DISCOVERY,
Journal Year:
2024,
Volume and Issue:
29(8), P. 100189 - 100189
Published: Nov. 4, 2024
Language: Английский
A coronaviral pore-replicase complex links RNA synthesis and export from double-membrane vesicles
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(45)
Published: Nov. 8, 2024
Coronavirus-infected
cells
contain
double-membrane
vesicles
(DMVs)
that
are
key
for
viral
RNA
replication
and
transcription,
perforated
by
hexameric
pores
connecting
the
vesicular
lumen
to
cytoplasm.
How
form
traverse
two
membranes,
how
DMVs
organize
synthesis,
is
unknown.
Using
structure
prediction
functional
assays,
we
show
nonstructural
membrane
protein
nsp4
pore
organizer,
spanning
double
forming
most
of
lining.
Nsp4
interacts
with
nsp3
on
cytoplasmic
side
replicase
inside
DMV.
Newly
synthesized
mRNAs
exit
DMV
into
cytoplasm,
passing
through
a
narrow
ring
conserved
residues.
Steric
constraints
imposed
predict
modified
nucleobases
block
mRNA
transit,
resulting
in
broad-spectrum
anticoronaviral
activity.
Language: Английский
A Coronaviral Pore-Replicase Complex Drives RNA Synthesis in Double Membrane Vesicles
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 18, 2024
Abstract
Coronavirus-infected
cells
contain
double-membrane
vesicles
(DMVs)
that
are
key
for
viral
RNA
replication
and
transcription,
perforated
by
hexameric
pores
connecting
the
vesicular
lumen
to
cytoplasm.
How
form
traverse
two
membranes,
how
DMVs
organize
synthesis,
is
unknown.
Using
structure
prediction
functional
assays,
we
show
non-structural
membrane
protein
nsp4
DMV
pore
organizer,
spanning
double
forming
most
of
lining.
Nsp4
interacts
with
nsp3
on
cytoplasmic
side
replicase
inside
DMV.
Newly
synthesized
mRNAs
exit
into
cytoplasm,
passing
through
a
narrow
ring
conserved
residues.
Steric
constraints
imposed
predict
modified
nucleobases
block
mRNA
transit,
broad
spectrum
anti-coronaviral
activity.
Language: Английский