bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 20, 2024
Abstract
The
growing
body
of
experimental
and
computational
studies
suggested
that
the
cross-neutralization
antibody
activity
against
Omicron
variants
may
be
driven
by
balance
tradeoff
multiple
energetic
factors
interaction
contributions
evolving
escape
hotspots
involved
in
antigenic
drift
convergent
evolution.
However,
dynamic
details
quantifying
contribution
these
factors,
particularly
balancing
nature
specific
interactions
formed
antibodies
with
epitope
residues
remain
scarcely
characterized.
In
this
study,
we
performed
molecular
dynamics
simulations,
ensemble-based
deep
mutational
scanning
SARS-CoV-2
spike
binding
free
energy
computations
for
two
distinct
groups
broadly
neutralizing
:
E1
group
(BD55-3152,
BD55-3546
BD5-5840)
F3
(BD55-3372,
BD55-4637
BD55-5514).
Using
approaches,
examine
determinants
which
potent
can
largely
evade
immune
resistance.
Our
analysis
revealed
emergence
a
small
number
positions
correspond
to
R346
K444
strong
van
der
Waals
act
synchronously
leading
large
contribution.
According
our
results,
Abs
effectively
exploit
hotspot
clusters
hydrophobic
sites
critical
functions
along
selective
complementary
targeting
positively
charged
are
important
ACE2
binding.
Together
conserved
epitopes,
lead
expanded
neutralization
breadth
resilience
shift
associated
viral
results
study
demonstrate
excellent
qualitative
agreement
between
predicted
mutations
respect
latest
experiments
on
average
scores.
We
argue
epitopes
leverage
stability
binding,
while
tend
emerge
synergistically
electrostatic
interactions.
During
the
three
years
following
emergence
of
COVID-19
pandemic,
African
continent,
like
other
regions
world,
was
significantly
impacted
by
COVID-19.
In
Morocco,
pandemic
has
been
marked
and
spread
several
SARS-CoV-2
variants,
leading
to
a
substantial
increase
in
incidence
infections
deaths.
Nevertheless,
there
persistent
lack
comprehensive
understanding
regarding
genetic
diversity,
evolution,
epidemiology
viral
lineages.
The
aim
this
study
analyze
diversity
identify
distinct
lineages,
as
well
assess
their
evolution
during
using
genomic
approaches.
Furthermore,
key
mutations
functional
proteins
across
different
lineages
were
highlighted
along
with
an
analysis
relationships
amongst
these
strains
better
understand
evolutionary
pathways.
A
total
2274
sequences
SARS-CoV-2,
acquired
from
Morocco
period
2020
2023,
extracted
GISAID
EpiCoV
database
subjected
analysis.
Lineages
clades
classified
according
nomenclature
GISAID,
Nextstrain,
Pangolin.
conducted
reported
accordance
STROBE
(Strengthening
Reporting
Observational
Studies
Epidemiology)
guidelines.
An
exhaustive
led
identification
157
PANGO
including
notable
such
B.1,
B.1.1,
B.1.528
B.1.177,
variants
B.1.1.7,
B.1.621,
B.1.525,
B.1.351,
B.1.617.1,
B.1.617.2
its
sub-lineages
AY.33,
AY.72,
AY.112,
AY.121
that
evolved
over
time
before
being
supplanted
Omicron
December
2021.
Among
analyzed,
sub-variants
had
prevalence
59.5%.
most
predominant
21K,
21L,
22B,
which
are
respectively
related
phylogenetically
BA.1,
BA.2,
BA.5.
June
2022,
rapidly
observed
recrudescence
cases
infection,
concurrent
coexistence
subvariants
clade
22B
BA.5.2.20,
BA.5,
BA.5.1,
BA.5.2.1,
BF.5,
supplanting
BA.1
(Clade
display
21K)
BA.2
21L),
became
marginal.
However,
XBB
(clade
22F)
progeny
XBB.1.5(23A),
XBB.1.16(23B),
CH.1.1(23C),
XBB.1.9(23D),
XBB.2.3(23E),
EG.5.1(23F),
XBB.1.5.70
(23G)
have
sporadically.
mutations,
H69del/V70del,
G142D,
K417N,
T478K,
E484K,
E484A,
L452R,
F486P,
N501Y,
Q613H,
D614G,
P681H/R,
known
for
implications
transmissibility
infectivity
ability
escape
antibodies,
identified.
This
identified
various
involved
Moroccan
isolates,
analyzed
trends.
genetically
closely
linked
original
highlighting
importance
maintaining
continuous
surveillance
extending
vaccination
coverage
prevent
new
could
potentially
be
more
infectious.
These
findings
also
provide
robust
basis
role
transmission,
immune
evasion,
reinfection.
During
the
three
years
following
emergence
of
COVID-19
pandemic,
African
continent,
like
other
regions
world,
was
substantially
impacted
by
COVID-19.
In
Morocco,
pandemic
has
been
marked
and
spread
several
SARS-CoV-2
variants,
leading
to
a
substantial
increase
in
incidence
infections
deaths.
Nevertheless,
there
persistent
lack
comprehensive
understanding
regarding
genetic
diversity,
evolution,
epidemiology
viral
lineages.
This
study
sought
deepen
genomic
through
retrospective
analysis.The
main
objective
this
analyze
diversity
identify
distinct
lineages,
as
well
assess
their
evolution
during
using
approaches.Furthermore,
key
mutations
functional
proteins
across
different
lineages
were
highlighted
along
with
an
analysis
relationships
amongst
these
strains
better
understand
evolutionary
pathways.
A
total
2274
sequences
SARS-CoV-2,
acquired
from
Morocco
period
2020
2023,
extracted
GISAID
EpiCoV
database
subjected
analysis.
Lineages
clades
classified
according
nomenclature
GISAID,
Nextstrain,
Pangolin.
The
conducted
reported
accordance
STROBE
(Strengthening
Reporting
Observational
Studies
Epidemiology)
guidelines.
An
exhaustive
led
identification
157
PANGO
including
notable
such
B.1,
B.1.1,
B.1.528
B.1.177,
variants
B.1.1.7,
B.1.621,
B.1.525,
B.1.351,
B.1.617.1,
B.1.617.2
its
sub-lineages
AY.33,
AY.72,
AY.112,
AY.121
that
evolved
over
time
before
being
supplanted
Omicron
December
2021.
Among
analyzed,
sub-variants
had
prevalence
59.5%.
most
predominant
21K,
21L,
22B,
which
are
respectively
related
phylogenetically
BA.1,
BA.2,
BA.5.
June
2022,
rapidly
observed
recrudescence
cases
infection,
concurrent
coexistence
subvariants
clade
22B
BA.5.2.20,
BA.5,
BA.5.1,
BA.5.2.1,
BF.5,
supplanting
BA.1
(Clade
display
21K)
BA.2
21L),
became
marginal.
However,
XBB
(clade
22F)
progeny
XBB.1.5(23A),
XBB.1.16(23B),
CH.1.1(23C),
XBB.1.9(23D),
XBB.2.3(23E),
EG.5.1(23F),
XBB.1.5.70
(23G)
have
sporadically.
Furthermore,
mutations,
H69del/V70del,
G142D,
K417N,
T478K,
E484K,
E484A,
L452R,
F486P,
N501Y,
Q613H,
D614G,
P681H/R,
known
for
implications
transmissibility
infectivity
ability
escape
antibodies,
identified.
identified
various
involved
Moroccan
isolates,
analyzed
trends.
genetically
closely
linked
original
highlighting
importance
maintaining
continuous
surveillance
expansion
vaccine
coverage
would
help
protect
patients
against
more
severe
clinical
disease.
These
findings
also
provide
robust
basis
role
transmission,
immune
evasion,
reinfection.
The
Omicron
variant
of
SARS-CoV-2,
which
is
a
cause
concern,
has
various
mutations
in
its
spike
protein.
This
protein
responsible
for
both
viral
infection
and
immunity.
We
have
analyzed
particular
sub-lineage
Omicron,
designated
XBB,
undergone
structural
functional
changes
as
response
to
the
African
selection
pressures.
Using
molecular
modeling,
we
compared
S
structures
XBB
discovered
that
reduced
receptor-binding
domain
(RBD)
because
loss
some
β-sheets.
change
may
result
an
increased
affinity
towards
human
angiotensin-converting
enzyme
2
(hACE2)
receptor.
also
conducted
recombination
analysis
sequences
using
Fast
Unconstrained
Bayesian
Approximation
(FUBAR)
Recombination
Detection
Program
4
(RDP
4).
Our
detected
signals
positive
N-terminal
(NTD)
S1
subunit,
contains
antibody-binding
epitopes,
RBD,
involved
entry.
findings
reveal
adaptation
Africa
potential
implications
pathogenesis
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 20, 2024
Abstract
The
growing
body
of
experimental
and
computational
studies
suggested
that
the
cross-neutralization
antibody
activity
against
Omicron
variants
may
be
driven
by
balance
tradeoff
multiple
energetic
factors
interaction
contributions
evolving
escape
hotspots
involved
in
antigenic
drift
convergent
evolution.
However,
dynamic
details
quantifying
contribution
these
factors,
particularly
balancing
nature
specific
interactions
formed
antibodies
with
epitope
residues
remain
scarcely
characterized.
In
this
study,
we
performed
molecular
dynamics
simulations,
ensemble-based
deep
mutational
scanning
SARS-CoV-2
spike
binding
free
energy
computations
for
two
distinct
groups
broadly
neutralizing
:
E1
group
(BD55-3152,
BD55-3546
BD5-5840)
F3
(BD55-3372,
BD55-4637
BD55-5514).
Using
approaches,
examine
determinants
which
potent
can
largely
evade
immune
resistance.
Our
analysis
revealed
emergence
a
small
number
positions
correspond
to
R346
K444
strong
van
der
Waals
act
synchronously
leading
large
contribution.
According
our
results,
Abs
effectively
exploit
hotspot
clusters
hydrophobic
sites
critical
functions
along
selective
complementary
targeting
positively
charged
are
important
ACE2
binding.
Together
conserved
epitopes,
lead
expanded
neutralization
breadth
resilience
shift
associated
viral
results
study
demonstrate
excellent
qualitative
agreement
between
predicted
mutations
respect
latest
experiments
on
average
scores.
We
argue
epitopes
leverage
stability
binding,
while
tend
emerge
synergistically
electrostatic
interactions.