PLoS Computational Biology,
Journal Year:
2022,
Volume and Issue:
18(5), P. e1010121 - e1010121
Published: May 12, 2022
The
nucleocapsid
(N)
protein
of
the
SARS-CoV-2
virus,
causal
agent
COVID-19,
is
a
multifunction
phosphoprotein
that
plays
critical
roles
in
virus
life
cycle,
including
transcription
and
packaging
viral
RNA.
To
play
such
diverse
roles,
N
has
two
globular
RNA-binding
modules,
N-
(NTD)
C-terminal
(CTD)
domains,
which
are
connected
by
an
intrinsically
disordered
region.
Despite
wealth
structural
data
available
for
isolated
NTD
CTD,
how
these
domains
arranged
full-length
oligomerization
influences
its
activity
remains
largely
unclear.
Herein,
using
experimental
from
electron
microscopy
biochemical/biophysical
techniques
combined
with
molecular
modeling
dynamics
simulations,
we
show
that,
absence
RNA,
formed
structurally
dynamic
dimers,
CTD
extended
conformations.
However,
presence
assumed
more
compact
conformation
where
packed
together.
We
also
provided
octameric
model
bound
to
RNA
consistent
images
Together,
our
results
shed
new
light
on
higher-order
oligomeric
structure
this
versatile
protein.
Genes,
Journal Year:
2023,
Volume and Issue:
14(2), P. 407 - 407
Published: Feb. 4, 2023
The
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
produced
diverse
molecular
variants
during
its
recent
expansion
in
humans
that
caused
different
transmissibility
and
severity
of
the
associated
disease
as
well
resistance
to
monoclonal
antibodies
polyclonal
sera,
among
other
treatments.
In
order
understand
causes
consequences
observed
SARS-CoV-2
diversity,
a
variety
studies
investigated
evolution
this
virus
humans.
general,
evolves
with
moderate
rate
evolution,
10
PLoS Pathogens,
Journal Year:
2023,
Volume and Issue:
19(1), P. e1011128 - e1011128
Published: Jan. 23, 2023
Coronavirus
disease
2019
is
a
respiratory
infectious
caused
by
the
severe
acute
syndrome
coronavirus
2
(SARS-CoV-2).
Evidence
on
pathogenesis
of
SARS-CoV-2
accumulating
rapidly.
In
addition
to
structural
proteins
such
as
Spike
and
Envelope,
functional
roles
non-structural
accessory
in
regulating
viral
life
cycle
host
immune
responses
remain
be
understood.
Here,
we
show
that
open
reading
frame
8
(ORF8)
acts
messenger
for
inter-cellular
communication
between
alveolar
epithelial
cells
macrophages
during
infection.
Mechanistically,
ORF8
secretory
protein
can
secreted
infected
via
both
conventional
unconventional
pathways.
Conventionally
glycosylated
loses
ability
recognize
interleukin
17
receptor
A
macrophages,
possibly
due
steric
hindrance
imposed
N-glycosylation
at
Asn78.
However,
unconventionally
does
not
undergo
glycosylation
without
experiencing
ER-Golgi
trafficking,
thereby
activating
downstream
NF-κB
signaling
pathway
facilitating
burst
cytokine
release.
Furthermore,
deletion
attenuates
inflammation
yields
less
lung
lesions
hamsters.
Our
data
collectively
highlights
role
development
storms
PLoS Biology,
Journal Year:
2025,
Volume and Issue:
23(1), P. e3002982 - e3002982
Published: Jan. 21, 2025
Coronaviruses
express
their
structural
and
accessory
genes
via
a
set
of
subgenomic
RNAs,
whose
synthesis
is
directed
by
transcription
regulatory
sequences
(TRSs)
in
the
5′
genomic
leader
upstream
each
body
open
reading
frame.
In
SARS-CoV-2,
TRS
has
consensus
AAACGAAC;
upon
searching
for
emergence
this
motif
global
SARS-CoV-2
sequences,
we
find
that
it
evolves
frequently,
especially
3′
end
genome.
We
show
well-supported
examples
Spike
gene—within
nsp16
coding
region
ORF1b—which
expressed
during
human
infection,
canonical
Envelope
gene
TRS,
both
which
have
evolved
convergently
multiple
lineages.
The
most
frequent
neo-TRS
within
Nucleocapsid
gene,
present
virtually
all
viruses
from
B.1.1
lineage,
including
variants
concern
Alpha,
Gamma,
Omicron
descendants
thereof.
Here,
demonstrate
leads
to
expression
novel
mRNA
encoding
truncated
C-terminal
portion
Nucleocapsid,
an
antagonist
type
I
interferon
production
contributes
viral
fitness
infection.
observe
distinct
phenotypes
when
sequence
mutated
compared
alone
ablated.
Our
findings
undergoing
evolutionary
changes
at
functional
RNA
level
addition
amino
acid
level.
PLoS Computational Biology,
Journal Year:
2022,
Volume and Issue:
18(5), P. e1010121 - e1010121
Published: May 12, 2022
The
nucleocapsid
(N)
protein
of
the
SARS-CoV-2
virus,
causal
agent
COVID-19,
is
a
multifunction
phosphoprotein
that
plays
critical
roles
in
virus
life
cycle,
including
transcription
and
packaging
viral
RNA.
To
play
such
diverse
roles,
N
has
two
globular
RNA-binding
modules,
N-
(NTD)
C-terminal
(CTD)
domains,
which
are
connected
by
an
intrinsically
disordered
region.
Despite
wealth
structural
data
available
for
isolated
NTD
CTD,
how
these
domains
arranged
full-length
oligomerization
influences
its
activity
remains
largely
unclear.
Herein,
using
experimental
from
electron
microscopy
biochemical/biophysical
techniques
combined
with
molecular
modeling
dynamics
simulations,
we
show
that,
absence
RNA,
formed
structurally
dynamic
dimers,
CTD
extended
conformations.
However,
presence
assumed
more
compact
conformation
where
packed
together.
We
also
provided
octameric
model
bound
to
RNA
consistent
images
Together,
our
results
shed
new
light
on
higher-order
oligomeric
structure
this
versatile
protein.