ORF8
is
an
asymmetric-homodimer
SARS-COV-2
accessory
protein
implicated
in
excesive
human
inflammation
causing
numerous
deaths.
There
no
approved
drug
targeting
ORF8,
nor
it
known
whether
any
anti-ORF8
drugs
could
reduce
inflammation.
Computationally
combining
ligand
co-evolution
of
parent
molecules
with
affinity-consensus
docking,
children
candidates
for
docking
to
cavities
were
generated.
Targeting
the
homodimer
interface
highest
affinity
scaffolds,
hundreds
grandchildren
predicting
nanoMolar
affinities,
unique
high
specificities
and
low
toxicity
risks
Although
remaining
hypothetical
without
experimental
confirmation,
this
constitute
a
new
methodological
attempt
search
drug-like
interfere
SARS-COV-2-dependent
excessive
Cellular and Molecular Immunology,
Journal Year:
2023,
Volume and Issue:
21(2), P. 171 - 183
Published: Nov. 20, 2023
Abstract
An
ancient
conflict
between
hosts
and
pathogens
has
driven
the
innate
adaptive
arms
of
immunity.
Knowledge
about
this
interplay
can
not
only
help
us
identify
biological
mechanisms
but
also
reveal
pathogen
vulnerabilities
that
be
leveraged
therapeutically.
The
humoral
response
to
SARS-CoV-2
infection
been
focus
intense
research,
role
immune
system
received
significantly
less
attention.
Here,
we
review
current
knowledge
various
means
employs
evade
defense
systems.
We
consider
immunity
in
vaccines
phenomenon
long
COVID.
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.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: April 13, 2024
Knockout
of
the
ORF8
protein
has
repeatedly
spread
through
global
viral
population
during
SARS-CoV-2
evolution.
Here
we
use
both
regional
and
pathogen
sequencing
to
explore
selection
pressures
underlying
its
loss.
In
Washington
State,
identified
transmission
clusters
with
knockout
throughout
evolution,
not
just
on
novel,
high
fitness
backbones.
Indeed,
is
truncated
more
frequently
knockouts
circulate
for
longer
than
any
other
gene.
Using
a
phylogeny,
find
evidence
positive
explain
this
phenomenon:
nonsense
mutations
resulting
in
shortened
products
occur
are
associated
faster
clade
growth
rates
synonymous
ORF8.
Loss
also
reduced
clinical
severity,
highlighting
diverse
impacts
Viruses,
Journal Year:
2024,
Volume and Issue:
16(1), P. 161 - 161
Published: Jan. 22, 2024
Severe
cases
of
SARS-CoV-2
infection
are
characterized
by
an
immune
response
that
leads
to
the
overproduction
pro-inflammatory
cytokines,
resulting
in
lung
damage,
cardiovascular
symptoms,
hematologic
acute
kidney
injury
and
multiple
organ
failure
can
lead
death.
This
remarkable
increase
cytokines
other
inflammatory
molecules
is
primarily
caused
viral
proteins,
particular
interest
has
been
given
ORF8,
a
unique
accessory
protein
specific
SARS-CoV-2.
Despite
plenty
research,
precise
mechanisms
which
ORF8
induces
proinflammatory
not
clear.
Our
investigations
demonstrated
augments
production
IL-6
induced
Poly(I:C)
human
embryonic
(HEK)-293
monocyte-derived
dendritic
cells
(mono-DCs).
We
discuss
our
findings
multifaceted
roles
as
modulator
cytokine
response,
focusing
on
type
I
interferon
IL-6,
key
component
In
addition,
we
explore
hypothesis
may
act
through
pattern
recognition
receptors
dsRNA
such
TLRs.
BMC Genomics,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: April 17, 2024
Abstract
Objective
This
study
aims
to
analyze
the
molecular
characteristics
of
novel
coronavirus
(SARS-CoV-2)
Omicron
variant
BA.2.76
in
Jining
City,
China.
Methods
Whole-genome
sequencing
was
performed
on
87
cases
SARS-CoV-2
infection.
Evolutionary
trees
were
constructed
using
bioinformatics
software
sequence
homology,
sites,
N-glycosylation
and
phosphorylation
sites.
Results
All
whole-genome
sequences
classified
under
evolutionary
branch
BA.2.76.
Their
similarity
reference
strain
Wuhan-Hu-1
ranged
from
99.72
99.74%.
In
comparison
Wuhan-Hu-1,
exhibited
77–84
nucleotide
differences
27
deletions.
A
total
69
amino
acid
9
deletions,
1
stop
codon
mutation
identified
across
18
proteins.
Among
them,
spike
(S)
protein
highest
number
ORF8
showed
a
Q27
mutation.
Multiple
proteins
displayed
variations
glycosylation
Conclusion
continues
evolve,
giving
rise
new
strains
with
enhanced
transmission,
stronger
immune
evasion
capabilities,
reduced
pathogenicity.
The
application
high-throughput
technologies
epidemic
prevention
control
COVID-19
provides
crucial
insights
into
virus
at
genomic
level,
thereby
holding
significant
implications
for
pandemic.
The Journal of Immunology,
Journal Year:
2023,
Volume and Issue:
211(2), P. 252 - 260
Published: June 2, 2023
Abstract
SARS-CoV-2
has
caused
an
estimated
7
million
deaths
worldwide
to
date.
A
secreted
accessory
protein,
known
as
open
reading
frame
8
(ORF8),
elicits
inflammatory
pulmonary
cytokine
responses
and
is
associated
with
disease
severity
in
COVID-19
patients.
Recent
reports
proposed
that
ORF8
mediates
downstream
signals
macrophages
monocytes
through
the
IL-17
receptor
complex
(IL-17RA,
IL-17RC).
However,
generally
are
found
be
restricted
nonhematopoietic
compartment,
thought
due
rate-limiting
expression
of
IL-17RC.
Accordingly,
we
revisited
capacity
induce
gene
mouse
human
monocytes.
In
SARS-CoV-2–infected
lungs,
IL17RC
mRNA
was
undetectable
monocyte/macrophage
populations.
cultured
macrophages,
but
not
led
elevated
target
cytokines.
ORF8-induced
signaling
fully
preserved
presence
anti–IL-17RA/RC
neutralizing
Abs
Il17ra−/−
cells.
also
operative
Il1r1−/−
bone
marrow–derived
macrophages.
TLR/IL-1R
family
adaptor
MyD88,
which
dispensable
for
IL-17R
signaling,
required
activity
yet
MyD88
signaling.
Thus,
conclude
transduces
via
independently
IL-17R.
Microorganisms,
Journal Year:
2024,
Volume and Issue:
12(3), P. 467 - 467
Published: Feb. 26, 2024
The
genome
of
severe
acute
respiratory
coronavirus-2
(SARS-CoV-2),
the
virus
responsible
for
coronavirus
disease
2019
(COVID-19),
has
undergone
a
rapid
evolution,
resulting
in
emergence
multiple
SARS-CoV-2
variants
with
amino
acid
changes.
This
study
aimed
to
sequence
whole
and
detect
present
specimens
from
Saudi
Arabia.
Furthermore,
we
sought
analyze
characterize
changes
various
proteins
identified
variants.
A
total
1161
samples
patients
diagnosed
COVID-19
Arabia,
between
1
April
2021
31
July
2023,
were
analyzed.
Whole
sequencing
was
employed
variant
identification
mutation
analysis.
statistical
analysis
performed
using
Statistical
Analytical
Software
SAS,
version
9.4,
GraphPad,
9.0.
twenty-three
subvariants
within
population,
Omicron
BA.1
(21K)
(37.0%)
Delta
(21J)
(12%)
being
most
frequently
detected.
Notably,
exhibited
higher
mean
rate.
Amino
mutations
observed
twelve
proteins.
Among
these,
spike
(S),
ORF1a,
nucleocapsid
(N),
ORF1b
showed
frequency
compared
other
viral
S
protein
highest
incidence
(47.6%).
Conversely,
ORF3a,
ORF8,
ORF7a,
ORF6,
ORF7b
appeared
more
conserved,
demonstrating
lowest
percentage
mutations.
investigation
structural
regions
revealed
N-terminal
S1
subunit
harbor
mutations,
while
domain
envelope
(E)
displayed
frequency.
provides
insights
into
genetic
diversity
SARS-CoV-2,
underscoring
need
further
research
comprehend
its
evolution
occurrence
These
findings
are
pertinent
development
testing
approaches,
therapeutics,
vaccine
strategies.
Journal of Molecular Recognition,
Journal Year:
2025,
Volume and Issue:
38(2)
Published: Feb. 5, 2025
ABSTRACT
Severe
acute
respiratory
syndrome
coronavirus
(SARS‐CoV),
the
virus
responsible
for
COVID‐19,
interacts
with
host
immune
system
through
complex
mechanisms
that
significantly
influence
disease
outcomes,
affecting
both
innate
and
adaptive
immunity.
These
interactions
are
crucial
in
determining
disease's
severity
host's
ability
to
clear
virus.
Given
virus's
substantial
socioeconomic
impact,
high
morbidity
mortality
rates,
public
health
importance,
understanding
these
is
essential.
This
article
examines
diverse
responses
triggered
by
SARS‐CoV‐2's
structural
proteins,
including
spike
(S),
membrane
(M),
envelope
(E),
nucleocapsid
(N)
along
nonstructural
proteins
(NSPs)
open
reading
frames.
play
pivotal
roles
modulation,
facilitating
viral
replication,
evading
detection,
contributing
severe
inflammatory
such
as
cytokine
storms
distress
(ARDS).
The
employs
strategies
like
suppressing
type
I
interferon
production
disrupting
key
antiviral
pathways,
MAVS,
OAS‐RNase‐L,
PKR.
study
also
explores
pathways
govern
activation
suppression
of
throughout
COVID‐19.
By
analyzing
sensing
receptors
initiated
upon
recognizing
SARS‐CoV‐2
this
review
elucidates
associated
response
Understanding
offers
valuable
insights
therapeutic
interventions
informs
strategies,
a
deeper
COVID‐19
immunopathogenesis.
Viruses,
Journal Year:
2025,
Volume and Issue:
17(4), P. 569 - 569
Published: April 15, 2025
SARS-CoV-2
has
demonstrated
a
remarkable
capacity
for
immune
evasion.
While
initial
studies
focused
on
the
Wuhan
variant
and
adaptive
immunity,
later
emerging
strains
such
as
Omicron
exhibit
mutations
that
may
alter
their
immune-modulatory
properties.
We
performed
comprehensive
review
of
evasion
mechanisms
associated
with
viral
proteins
to
focus
evolutionary
dynamics
modulation.
systematically
analyzed
compared
impact
all
currently
known
type
I
interferon
(IFN)
responses
using
dual-luciferase
reporter
assay
carrying
an
interferon-inducible
promoter.
Results
revealed
Nsp1,
Nsp5,
Nsp14,
ORF6
are
potent
IFN
inhibitors
conserved
across
strains.
Notably,
we
identified
strain-specific
differences,
Nsp6
Spike
exhibiting
enhanced
suppression
in
Omicron,
whereas
Envelope
protein
largely
retained
this
function.
To
extend
these
findings,
investigated
selected
primary
human
endothelial
cells
also
observed
differences
response
higher
expressing
strain
variant,
suggesting
Omicron’s
adaptational
contribute
damped
course
pandemic’s
trajectory.
The
unique
ORF8
is
an
asymmetric
homodimer
accessory
protein
of
SARS-COV-2
implicated
in
pathogenesis
by
activating
excesive
human
inflammation
causing
numerous
deaths.
There
no
approved
drug
targeting
ORF8,
nor
it
known
whether
any
anti-ORF8
drugs
could
reduce
coronavirus-induced
inflammation.
Computationally
combining
ligand
co-evolution
parent
molecules
with
affinity-ranking
consensus
docking,
children
candidates
for
cavities
and
ligands
were
generated.
Targeting
the
interface
cavity
highest
affinity
scaffolds,
hundreds
grandchildren
generated
specificity-toxicity
controlled
additional
co-evolutions
to
predict
nanoMolar
affinities,
high
specificities
low
toxicity
risks.
Although
remaining
hypothetical
without
experimental
confirmation,
these
constitute
a
new
methodological
attempt
search
drug-like
interfere
SARS-COV-2-dependent
excessive
