International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(3), P. 2488 - 2488
Published: Jan. 27, 2023
In
this
Special
Issue,
many
original
contributions
concerning
serological
methods
for
SARS-CoV-2
were
collected,
some
of
them
with
implications
about
therapeutics
[...].
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(3), P. 2264 - 2264
Published: Jan. 23, 2023
The
first
2
years
of
the
COVID-19
pandemic
were
mainly
characterized
by
recurrent
mutations
SARS-CoV-2
Spike
protein
at
residues
K417,
L452,
E484,
N501
and
P681
emerging
independently
across
different
variants
concern
(Alpha,
Beta,
Gamma,
Delta).
Such
homoplasy
is
a
marker
convergent
evolution.
Since
Spring
2022
third
year
pandemic,
with
advent
Omicron
its
sublineages,
evolution
has
led
to
observation
lineages
acquiring
an
additional
group
amino
acid
residues,
namely
R346,
K444,
N450,
N460,
F486,
F490,
Q493,
S494.
Mutations
these
have
become
increasingly
prevalent
during
Summer
Autumn
2022,
combinations
showing
increased
fitness.
most
likely
reason
for
this
convergence
selective
pressure
exerted
previous
infection-
or
vaccine-elicited
immunity.
accelerated
caused
failure
all
anti-Spike
monoclonal
antibodies,
including
bebtelovimab
cilgavimab.
While
we
are
learning
how
fast
coronaviruses
can
mutate
recombine,
should
reconsider
opportunities
economically
sustainable
escape-proof
combination
therapies,
refocus
antibody-mediated
therapeutic
efforts
on
polyclonal
preparations
that
less
allow
viral
immune
escape.
Viruses,
Journal Year:
2022,
Volume and Issue:
14(6), P. 1239 - 1239
Published: June 7, 2022
Recombination
is
a
common
evolutionary
tool
for
RNA
viruses,
and
coronaviruses
are
no
exception.
We
review
here
the
evidence
recombination
in
SARS-CoV-2
reconcile
nomenclature
recombinants,
discuss
their
origin
fitness,
speculate
how
recombinants
could
make
difference
future
of
COVID-19
pandemics.
Clinical Microbiology Reviews,
Journal Year:
2022,
Volume and Issue:
35(3)
Published: March 9, 2022
Convalescent
plasma
(CP)
recurs
as
a
frontline
treatment
in
epidemics
because
it
is
available
soon
there
are
survivors.
The
COVID-19
pandemic
represented
the
first
large-scale
opportunity
to
shed
light
on
mechanisms
of
action,
safety,
and
efficacy
CP
using
modern
evidence-based
medicine
approaches.
Studies
ranging
from
observational
case
series
randomized
controlled
trials
(RCTs)
have
reported
highly
variable
results
for
(CCP),
resulting
uncertainty.
We
analyzed
variables
associated
with
efficacy,
such
clinical
settings,
disease
severity,
CCP
SARS-CoV-2
(severe
acute
respiratory
syndrome
coronavirus
2)
antibody
levels
function,
dose,
timing
administration
(variously
defined
time
onset
symptoms,
molecular
diagnosis,
diagnosis
pneumonia,
or
hospitalization,
by
serostatus),
outcomes
(defined
requirement
ventilation,
improvement,
mortality),
provenance
collection,
criteria
efficacy.
conflicting
trial
results,
along
both
recent
WHO
guidelines
discouraging
usage
expansion
FDA
emergency
use
authorization
(EUA)
include
outpatient
CCP,
create
confusion
clinicians
patients
about
appropriate
CCP.
A
review
30
RCTs
demonstrated
that
signals
(including
reductions
mortality)
were
more
likely
if
neutralizing
titer
was
>160
randomization
less
than
9
days.
emergence
Omicron
variant
also
reminds
us
benefits
polyclonal
therapies,
especially
bridge
development
availability
specific
therapies.
Viruses,
Journal Year:
2022,
Volume and Issue:
14(2), P. 187 - 187
Published: Jan. 19, 2022
Sterilizing
immunity
after
vaccination
is
desirable
to
prevent
the
spread
of
infection
from
vaccinees,
which
can
be
especially
dangerous
in
hospital
settings
while
managing
frail
patients.
requires
neutralizing
antibodies
at
site
infection,
for
respiratory
viruses
such
as
SARS-CoV-2
implies
occurrence
IgA
mucosal
secretions.
Systemic
by
intramuscular
delivery
induces
no
or
low-titer
against
vaccine
antigens.
Mucosal
priming
boosting,
needed
provide
sterilizing
immunity.
On
other
side
coin,
immunity,
zeroing
interhuman
transmission,
could
confine
animal
reservoirs,
preventing
spontaneous
attenuation
virulence
humans
presumably
happened
with
endemic
coronaviruses.
We
review
here
pros
and
cons
each
strategy,
current
vaccines
under
development,
their
implications
public
health.
Pathogens,
Journal Year:
2022,
Volume and Issue:
11(8), P. 823 - 823
Published: July 22, 2022
Anti-Spike
monoclonal
antibodies
have
been
considered
a
promising
approach
to
COVID-19
therapy.
Unfortunately,
the
advent
of
resistant
lineages
jeopardized
their
effectiveness
and
prompted
limitations
in
clinical
use.
Change
dominant
variant
can
be
fast
such
an
extent
that,
absence
timely
medical
education,
prescribers
keep
using
these
drugs
for
relatively
long
periods
even
patients
with
variants.
Therefore,
many
could
exposed
unlikely
benefits
probable
risks.
We
show
here
that
about
20%
bamlanivimab+etesevimab,
30%
casirivimab+imdevimab,
sotrovimab
courses
were
administered
Italy
during
which
fully
was
dominant.
Additionally,
antibody
cocktails,
vast
majority
usage
occurred
against
variants
one
mAbs
within
cocktail
ineffective.
Given
high
costs
potential
side
effects,
it
would
important
consider
frequent
review
appropriateness
communication
when
benefit/risk
balance
is
no
longer
favorable.
Viruses,
Journal Year:
2023,
Volume and Issue:
15(5), P. 1048 - 1048
Published: April 25, 2023
Drug
appropriateness
is
a
pillar
of
modern
evidence-based
medicine,
but
the
turnaround
times
genomic
sequencing
are
not
compatible
with
urgent
need
to
deliver
treatments
against
microorganisms.
Massive
worldwide
surveillance
has
created
an
unprecedented
landscape
for
exploiting
viral
therapeutic
purposes.
When
it
comes
antiviral
antibodies,
using
IC
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: March 7, 2022
Severe
Acute
Respiratory
Syndrome
Coronavirus-2
(SARS-CoV-2)
marks
the
third
novel
β-coronavirus
to
cause
significant
human
mortality
in
last
two
decades.
Although
vaccines
are
available,
too
few
have
been
administered
worldwide
keep
virus
check
and
prevent
mutations
leading
immune
escape.
To
determine
if
antibodies
could
be
identified
with
universal
coronavirus
activity,
plasma
from
convalescent
subjects
was
screened
for
IgG
against
a
stabilized
pre-fusion
SARS-CoV-2
spike
S2
domain,
which
is
highly
conserved
between
β-coronavirus.
From
these
subjects,
several
S2-specific
monoclonal
(hmAbs)
were
developed
that
neutralized
recognition
of
all
variants
concern
(VoC)
tested
(Beta,
Gamma,
Delta,
Epsilon,
Omicron).
The
hmAb
1249A8
emerged
as
most
potent
broad
hmAb,
able
recognize
neutralize
SARS-CoV
MERS-CoV.
demonstrated
prophylactic
activity
K18
hACE2
mice
infected
lineage
A
B
Beta,
Omicron
VoC.
delivered
single
4
mg/kg
intranasal
(i.n.)
dose
hamsters
12
hours
following
infection
Delta
protected
them
weight
loss,
therapeutic
further
enhanced
when
combined
1213H7,
an
S1-specific
neutralizing
hmAb.
As
little
2
i.n.
Urbani
strain,
loss
significantly
reduced
upper
lower
respiratory
viral
burden.
These
results
indicate
vivo
cooperativity
S1
specific
hmAbs
mAbs
potential
can
induced
humans
guide
vaccine
development.
COVID,
Journal Year:
2022,
Volume and Issue:
2(5), P. 599 - 620
Published: May 12, 2022
The
COVID-19
pandemic
continues
to
cause
tremendous
loss
of
life
and
put
massive
strain
on
the
functioning
societies
worldwide.
Despite
cataclysmic
proportions
this
viral
outbreak,
as
yet,
no
effective
curative
treatment
is
available.
vaccines,
while
a
scientific
achievement
historical
proportions,
can
only
be
utilized
in
prophylaxis
require
vaccination
majority
given
population.
Convalescent
plasma
therapies
blood
group
testing
patient
hospitalization
are
difficult
into
place
scale
Monoclonal
antibodies
mass
produced
with
hybridoma
cell
culture
highly
specific
antigens.
What
more,
monoclonal
produce
far
more
reproducible
effects
than
other
approaches
active
immunization
further
enhanced
through
engineering.
Currently,
there
exist
two
use
antibodies,
each
several
currently
under
development
or
clinical
testing.
first
utilizes
which
target
spike
proteins
block
entry
host
mark
particles
for
destruction
by
immune
cells.
second
approach
that
neutralize
cytokines,
take
part
cytokine
release
syndrome,
responsible
many
most
damaging
symptoms
associated
COVID-19,
thus
reducing
systemic
inflammation
ultimately—patient
morbidity
mortality.
There
yet
remain
challenges
overcome
if
become
mainstream
therapeutic
agents
COVID-19.
this,
field
research
experiencing
forward
leap
exceptional
amount
data
gathered
so
serve
groundwork
widely
available
antiviral
antibody
treatments.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(4), P. 2078 - 2078
Published: Feb. 14, 2022
SARS-CoV-2
infection
elicits
a
polyclonal
neutralizing
antibody
(nAb)
response
that
primarily
targets
the
spike
protein,
but
it
is
still
unclear
which
nAbs
are
immunodominant
and
what
distinguishes
them
from
subdominant
nAbs.
This
information
would
however
be
crucial
to
predict
evolutionary
trajectory
of
virus
design
future
vaccines.
To
shed
light
on
this
issue,
we
gathered
83
structures
in
complex
with
protein
domains.
We
analyzed
silico
ability
these
bind
full
trimer
open
closed
conformations,
predicted
change
binding
affinity
most
frequently
observed
variants
circulating
strains.
led
us
define
four
nAb
classes
distinct
variant
escape
fractions.
By
comparing
fractions
those
measured
plasma
infected
patients,
showed
class
contributes
immune
able
its
conformation.
Although
only
partially
inhibits
host’s
angiotensin
converting
enzyme
2
(ACE2),
has
been
suggested
lock
pre-fusion
conformation
therefore
prevent
transition
an
state.
Furthermore,
comparison
our
predictions
mRNA-1273
vaccinated
patient
measurements
suggests
proteins
contained
vaccines
elicit
different
than
one
elicited
by
natural
highly
stable
closed-form
as
next-generation
vaccine
immunogens.
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: Sept. 15, 2021
Abstract
Convalescent
plasma
(CP)
recurs
as
a
frontline
treatment
in
epidemics
because
it
is
available
soon
there
are
survivors.
The
COVID-19
pandemic
represented
the
first
large-scale
opportunity
to
shed
light
into
mechanisms
of
action,
safety
and
efficacy
CP
using
modern
evidence-based
medicine
approaches.
Studies
ranging
from
observational
case
series
randomized
controlled
trials
(RCT)
have
reported
highly
variable
results
for
(CCP),
resulting
uncertainty.
Reasons
CCP
success
failure
may
be
hidden
study
details,
which
usually
difficult
explain
physicians
public
but
provide
fertile
ground
designing
next-generation
studies.
We
analyzed
variables
associated
with
such
clinical
settings,
disease
severity,
SARS-CoV-2
antibody
levels
function,
dose,
timing
administration
(variously
defined
time
onset
symptoms,
molecular
diagnosis,
diagnosis
pneumonia,
or
hospitalization,
by
serostatus),
outcomes
(defined
requirement
ventilation,
improvement
mortality),
provenance
collection,
criteria
efficacy.
Focusing
only
on
30
RCTs
we
noted
that
these
were
more
likely
show
signals
efficacy,
including
reductions
mortality,
if
neutralizing
titer
was
≥
160
randomization
≤
9
days,
consistent
passive
therapy
requiring
dosing
sufficient
antibody.
fact
most
studies
revealed
despite
variability
its
use
suggest
therapeutic
effects
become
apparent
data
noise.
Despite
recent
WHO
guidelines
discouraging
usage,
Omicron
variant
concern
reminding
us
superiority
polyclonal
therapies
over
monoclonal
antibodies,
vaccinated
convalescents
evaluated