bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
Abstract
Convergent
evolution
in
protein
antigens
is
common
across
pathogens
and
has
also
been
documented
SARS-CoV-2;
the
most
likely
reason
need
to
evade
selective
pressure
exerted
by
previous
infection-
or
vaccine-elicited
immunity.
There
a
pressing
for
tools
that
allow
automated
analysis
of
convergent
mutations.
In
response
this
need,
we
developed
ConvMut,
tool
identifying
patterns
recurrent
mutations
SARS-CoV-2
evolution.
To
end,
exploited
granular
phylogenetic
tree
representation
PANGO,
allowing
us
observe
what
call
deltas,
i.e.,
groups
are
acquired
on
top
immediately
upstream
nodes.
Deltas
comprise
both
amino
acid
substitutions
deletions.
ConvMut
can
perform
individual
identify
single
independently
given
subtree
(starting
from
user-selected
root).
Such
represented
barplot
be
sorted
frequency
position
filtered
region
interest.
Lineages
then
gathered
into
clusters
according
their
sets
shared
Finally,
an
interactive
graph
orders
clusters,
details
changes
each
sublineage,
allows
evolutive
path
until
selected
lineage.
Other
unique
paired
with
main
functionality
support
complete
analysis,
such
as
nucleotide
at
residue
subtree.
We
expect
will
facilitate
design
antiviral
anti-Spike
monoclonal
antibodies
Spike-based
vaccines
longer-lasting
efficacy,
minimizing
development
marketing
failures.
Pathogens and Immunity,
Год журнала:
2024,
Номер
10(1), С. 1 - 11
Опубликована: Сен. 30, 2024
First-generation
anti-SARS-CoV-2
monoclonal
antibodies
(mAbs)
used
for
prophylaxis
or
therapeutic
purposes
in
immunocompromised
patients
have
been
withdrawn
because
of
the
emergence
resistant
Omicron
variants.
In
2024,
2
novel
mAbs,
VYD222/Pemivibart
and
AZD3152/Sipavibart,
were
approved
by
health
authorities,
but
their
activity
against
contemporary
JN.1
sublineages
is
poorly
characterized.
Frontiers in Chemistry,
Год журнала:
2025,
Номер
13
Опубликована: Март 19, 2025
Introduction
Monoclonal
antibody
(mAb)
drug
treatments
have
proven
effective
in
reducing
COVID-19-related
hospitalizations
or
fatalities,
particularly
among
high-risk
patients.
Numerous
experimental
studies
explored
the
structures
of
spike
proteins
and
their
complexes
with
ACE2
mAbs.
These
3D
provide
crucial
insights
into
interactions
between
mAb,
forming
a
basis
for
development
diagnostic
tools
therapeutics.
However,
field
computational
biology
has
faced
substantial
challenges
due
to
lack
methods
precise
protein
structural
comparisons
accurate
prediction
molecular
interactions.
In
our
previous
studies,
we
introduced
Triangular
Spatial
Relationship
(TSR)-based
algorithm,
which
represents
protein’s
structure
using
vector
integers
(keys).
earlier
however,
were
limited
individual
proteins.
Purpose
This
study
introduces
new
extensions
TSR-based
enhancing
its
ability
two
molecules.
We
apply
these
gain
mechanistic
understanding
-
mAb
Method
expanded
basic
TSR
method
three
novel
ways:
(1)
keys
encompassing
all
atoms,
(2)
cross
molecules,
(3)
intra-residual
amino
acids.
representation
offers
unique
advantage
by
simplifying
search
similar
substructures
within
datasets.
Results
The
study’s
key
findings
include:
(i)
effectively
quantified
interpreted
conformational
changes
steric
effects
newly
keys.
(ii)
Six
clusters
CDRH3
CDRL3
identified
all-atom
(iii)
constructed
TSR-STRSUM
(TSR-STRucture
SUbstitution
Matrix),
matrix
that
pairwise
similarities
acid
structures,
providing
valuable
applications
sequence
comparison.
(iv)
Intra-residual
revealed
distinct
Tyr
characterized
specific
triangle
geometries.
Conclusion
presents
an
advanced
approach
not
only
quantifies
interprets
backbones,
entire
acids,
but
also
facilitates
induced
binding
across
some
instances,
direct
correlation
functions
was
successfully
established.
Clinical Infectious Diseases,
Год журнала:
2024,
Номер
79(6), С. 1404 - 1407
Опубликована: Авг. 8, 2024
Abstract
The
COVID-19
pandemic
witnessed
the
greatest
deployment
of
monoclonal
antibody
(mAb)
therapies
for
an
infectious
disease,
but
all
were
defeated
by
SARS-CoV-2
evolution.
As
new
mAbs
are
developed,
disease
community
needs
stewardship
practices
to
reduce
emergence
resistance.
Expert Review of Anti-infective Therapy,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
The
success
in
the
COVID-19
pandemic
containment
largely
originated
from
vaccine-
and
infection-elicited
immunity,
with
SARS-CoV-2
infection
only
marginally
mitigated
by
availability
of
antiviral
drugs.
current
lack
effective
prophylactic
therapeutic
agents
immunocompromised
patients
highlights
need
for
a
radical
change
design
both
drug
manufacturing
clinical
trials.
In
this
review
authors
summarize
their
suggestions
manufacturers,
reviewing
classes
small
molecule
antivirals
passive
immunotherapies
highlighting
limitations
unexploited
potential.
Molecular
serological
testing
can
improve
appropriateness.
Efficacy
be
improved
combining
different
while
preserving
economical
sustainability.
Respiratory
delivery
should
better
investigated
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 15, 2025
Abstract
Existing
technologies
employed
to
generate
antibodies
against
bacterial
polysaccharides
and
proteins
rely
on
the
availability
of
purified
or
synthetic
antigens.
Here
we
present
a
genetics-based
platform
that
utilises
Citrobacter
rodentium
(CR),
an
enteric
mouse
pathogen,
both
produce
complex
heterologous
polysaccharide
protein
antigens
during
natural
infection.
As
proof
concept,
use
lipopolysaccharide
(O1),
capsular
(K2)
type
3
fimbrial
(T3F)
expressed
by
WHO
critical
priority
pathogen
Klebsiella
pneumoniae
(KP).
Following
one
infection
cycle
(28
days)
CR
induces
specific
IgG
KPO1,
KPK2
KPT3F.
We
demonstrate
are
functional
in
downstream
applications
including
protection
pathogenic
KP
challenge,
serotyping
biofilm
inhibition.
Whilst
were
used
as
prototypical
examples,
this
modular
is
now
readily
adaptable
diverse
antigens,
with
basic
science,
public
health
therapeutic
applications.
Expert Opinion on Biological Therapy,
Год журнала:
2024,
Номер
24(8), С. 787 - 797
Опубликована: Авг. 1, 2024
Monoclonal
antibody
(mAb)
therapies
proved
safe
and
effective
in
preventing
progression
of
COVID-19
to
hospitalization,
but
most
were
eventually
defeated
by
continued
viral
evolution.
mAb
combinations
those
mAbs
that
deliberatively
selected
target
conserved
regions
the
SARS-CoV-2
spike
protein
more
resilient
escape
variants
as
evident
longer
clinical
useful
lives.