Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
Abstract
Therapeutic
monoclonal
antibodies
(mAbs)
against
SARS-CoV-2
become
obsolete
as
spike
substitutions
reduce
antibody
binding.
To
induce
conserved
receptor-binding
domain
(RBD)
regions
for
protection
variants
of
concern
and
zoonotic
sarbecoviruses,
we
developed
mosaic-8b
RBD-nanoparticles
presenting
eight
sarbecovirus
RBDs
arranged
randomly
on
a
60-mer
nanoparticle.
Mosaic-8b
immunizations
protected
animals
from
challenges
viruses
whose
were
matched
or
mismatched
to
those
nanoparticles.
Here,
describe
neutralizing
mAbs
mosaic-8b–immunized
rabbits,
some
par
with
Pemgarda
(the
only
currently
FDA-approved
therapeutic
mAb).
Deep
mutational
scanning,
in
vitro
selection
resistance
mutations,
cryo-EM
structures
spike-antibody
complexes
demonstrated
targeting
epitopes.
Rabbit
included
critical
D-gene
segment
features
common
human
anti-RBD
mAbs,
despite
rabbit
genomes
lacking
an
equivalent
segment.
Thus,
mosaic
RBD-nanoparticle
immunization
coupled
multiplexed
screening
represent
efficient
way
generate
select
pan-sarbecovirus
pan-SARS-2
variant
mAbs.
Язык: Английский
Sipavibart: when a success changes into a failure
The Lancet Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Development of antiviral drugs for COVID-19 in 2025: unmet needs and future challenges
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
Язык: Английский
Antiviral combination treatment strategies for SARS-CoV-2 infection in immunocompromised patients
Current Opinion in Infectious Diseases,
Год журнала:
2024,
Номер
37(6), С. 506 - 517
Опубликована: Окт. 23, 2024
Purpose
of
review
The
purpose
this
is
to
report
the
available
evidence
regarding
use
combination
regimens
antivirals
and/or
antibody-based
therapy
in
treatment
SARS-CoV-2
immunocompromised
patients.
Recent
findings
Literature
search
identified
24
articles,
excluding
single
case
reports,
which
included
mainly
patients
with
hematological
malignancies
B-cell
depletion.
Data
were
divided
based
on
timing
and
reason
for
administration
treatment,
that
is,
early
prevent
progression
severe
COVID-19
prolonged
or
relapsed
infection.
We
described
treated
populations,
duration
composition
treatment.
briefly
addressed
new
options
we
proposed
an
algorithm
management
infection
affected
by
malignancies.
Summary
Combination
seems
effective
(73–100%)
well
tolerated
(<5%
reported
bradycardia,
hepatotoxicity,
neutropenia)
strategy
treating
prolonged/relapsed
infections
host,
although
its
optimal
cannot
be
defined
currently
evidence.
role
as
at
a
high
risk
disease/persistent
shedding
requires
further
from
comparison
monotherapy,
even
though
efficacy
was
combinations
plus
mAbs
previous
viral
variants.
Язык: Английский