Impact of SARS-CoV-2 RBM Mutations N501Y and E484K on ACE2 Binding: A Combined Computational and Experimental Study
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(9), С. 4064 - 4064
Опубликована: Апрель 25, 2025
The
SARS-CoV-2
spike
receptor-binding
motif
is
crucial
for
viral
entry
via
interaction
with
the
human
ACE2
receptor.
Mutations
N501Y
and
E484K,
found
in
several
variants
of
concern,
impact
transmissibility
immune
escape,
but
experimental
data
on
their
binding
effects
remain
inconsistent.
Using
isothermal
titration
calorimetry
(ITC)
molecular
dynamics
(MD)
simulations,
we
analyzed
thermodynamic
structural
these
mutations.
ITC
confirmed
that
increases
affinity
by
2.2-fold,
while
E484K
enhances
5.8-fold.
Beta/Gamma
variant
(carrying
both
mutations)
showed
strongest
affinity,
a
15-fold
increase.
was
enthalpy-driven,
introduced
entropy-driven
effects,
suggesting
hydrophobic
interactions
conformational
changes.
MD
simulations
revealed
distinct
poses,
peptides
interacting
secondary
site.
A
strong
correlation
between
entropy
contributions
contacts.
Additionally,
convolutional
neural
network
used
to
estimate
free
energy
complexes.
Our
findings
confirm
enhance
binding,
greatest
effect
when
combined,
providing
insights
into
evolution
potential
therapeutic
strategies.
Язык: Английский
Exploring Key Biomarkers and Common Pathogenesis of Seven Digestive System Cancers and Their Correlation with COVID-19
Current Issues in Molecular Biology,
Год журнала:
2023,
Номер
45(7), С. 5515 - 5533
Опубликована: Июнь 30, 2023
Digestive
system
cancer
and
COVID-19
significantly
affect
the
digestive
system,
but
mechanism
of
interaction
between
cancers
has
not
been
fully
elucidated.
We
downloaded
gene
expression
seven
(oral,
esophageal,
gastric,
colorectal,
hepatocellular,
bile
duct,
pancreatic)
from
GEO
identified
hub
differentially
expressed
genes.
Multiple
verifications,
diagnostic
efficacy,
prognostic
analysis,
functional
enrichment
related
transcription
factors
genes
were
explored.
23
common
DEGs
for
subsequent
analysis.
CytoHubba
nine
(CCNA2,
CCNB1,
CDKN3,
ECT2,
KIF14,
KIF20A,
KIF4A,
NEK2,
TTK).
TCGA
data
validated
excellent
ability
Functional
analysis
revealed
that
processes
cell
division
cycle
essential
in
cancers.
Furthermore,
six
(E2F1,
E2F3,
E2F4,
MYC,
TP53,
YBX1)
involved
regulation.
Via
vitro
experiments,
CCNA2,
MYC
was
verified
25
colorectal
tissue
pairs.
Our
study
key
biomarks
pathogenesis
COVID-19.
These
may
provide
new
ideas
further
mechanistic
research.
Язык: Английский
Cardiovascular and mental symptoms of post-COVID-19 syndrome as a possible consequence of the bradykinin storm: A clinical case
Polish Annals of Medicine,
Год журнала:
2024,
Номер
unknown, С. 1 - 6
Опубликована: Фев. 1, 2024
Introduction
Although
as
of
today,
the
hypothesis
bradykinin
storm
in
COVID-19
cannot
be
directly
confirmed,
many
theoretical
assumptions
and
empirical
data
support
its
validity.
Aim
The
purpose
this
article
is,
using
example
a
clinical
case,
to
draw
attention
need
for
further
study
pathogenesis
manifestations
post-COVID-19
syndrome,
considering
assessment
various
theories,
including
hypothesis.
Case
We
analysed
from
young
male
patient
with
syndrome
who
referred
consultant
expressed
complaints
palpitation,
blood
pressure
increase,
muscle
weakness,
feeling
fear,
hypochondria,
sleep
disturbances,
reduced
working
performance.
Results
discussion
found
high
degree
autonomic
dysregulation
(predominantly
sympathetic
hyperactivation),
anxiety,
disorder.
There
was
no
hypertension,
though
ambulatory
monitoring
allowed
determine
status
non-dipper.
Patient's
tests
after
revealed
decrease
plasma
level
aldosterone,
significant
increase
both
homocysteine
free
cortisol
urine,
mild
transient
isolated
triiodothyronine.
All
abnormal
test
parameters
turned
normal
3
months
onset
COVID-19.
assume
that
symptoms
changes
number
laboratory
presented
case
may
associated
effects
storm.
Conclusions
This
suggests
continuing
about
potential
role
course
syndrome.
Язык: Английский
Comprehensive Review of COVID-19: Symptoms, Diagnosis, and Management
Austin Journal of Autism & Related Disabilities,
Год журнала:
2024,
Номер
10(1)
Опубликована: Фев. 9, 2024
COVID-19,
caused
by
the
novel
coronavirus
SARS-CoV-2,
can
lead
to
a
wide
range
of
symptoms,
varying
from
mild
severe.
Common
symptoms
include
fever,
cough,
and
shortness
breath.
Other
may
fatigue,
muscle
or
body
aches,
headache,
loss
taste
smell,
sore
throat,
congestion
runny
nose,
nausea
vomiting,
diarrhea.
Some
individuals
also
experience
more
severe
such
as
difficulty
breathing,
chest
pain
pressure,
confusion,
inability
stay
awake,
bluish
lips
face,
which
require
immediate
medical
attention.
It’s
important
note
that
appear
2-14
days
after
exposure
virus,
some
remain
asymptomatic
carriers.
If
you
suspect
have
COVID-19
been
exposed
it’s
crucial
seek
advice
follow
public
health
guidelines
prevent
spread
virus.
diagnosis
involves
identifying
presence
SARS-CoV-2
virus
through
various
methods
RT-PCR
testing,
antigen
antibody
imaging
techniques
X-rays
CT
scans.
Early
accurate
is
for
effective
management
control
disease.
Rapid
widespread
along
with
proper
isolation
contact
tracing,
are
essential
containing
multifaceted
approach,
including
vaccination,
measures
mask-wearing
social
distancing.
Treatment
focuses
on
supportive
care
and,
in
cases,
antiviral
medications.
On-going
research
developing
strategies
mitigate
its
impact
health.
Язык: Английский
INFLUENCE OF COMORBIDITIES ON THE SEVERITY OF COVID-19
Сергей Григорьевич Щербак,
Андрей Михайлович Сарана,
Анна Юрьевна Анисенкова
и другие.
University therapeutic journal,
Год журнала:
2024,
Номер
6(1), С. 26 - 48
Опубликована: Июнь 17, 2024
Уже
в
начале
пандемии
было
замечено
влияние
сопутствующих
заболеваний
на
степень
тяжести
и
исходы
COVID-19.
С
тех
пор
большое
внимание
сосредоточено
проблемах
коморбидности,
связанных
с
инфекцией
SARS-CoV-2,
долгосрочными
последствиями
Хронические
заболевания,
которые
нарушают
гомеостаз
организма,
делают
пациентов
более
склонными
к
инфекциям.
Наличие
хронических
ассоциировано
высокой
степенью
COVID-19
высоким
риском
смерти
от
данной
инфекции.
Помимо
респираторных
осложнений,
новая
коронавирусная
инфекция
связана
повышенным
сердечно-сосудистых
событий,
таких
как
сердечные
приступы,
инфаркты,
инсульты
тромбозы.
Пациенты
ранее
существовавшими
артериальной
гипертензией,
сердечно-сосудистыми
заболеваниями,
диабетом
ожирением
особенно
восприимчивы
этим
осложнениям.
У
пациентов,
инфицированных
вирусом
наиболее
распространенными
сопутствующими
хроническими
влияющими
развитие
прогноз,
являются
метаболические
расстройства,
такие
метаболический
синдром,
ожирение,
гиперлипидемия
диабет,
а
также
сердечно-сосудистые
заболевания
артериальная
гипертензия.
Патофизиологические
механизмы
метаболических
имеют
своей
основе
много
общего
коронавирусной
инфекцией.
Вирус
SARSCoV2
способен
напрямую
повреждать
сердце
сосудистый
эндотелий
вызывать
системную
воспалительную
реакцию
протромботическое
состояние,
усугубляют
сопутствующие
заболевания.
многих
пожилого
возраста,
имеются
анамнезе
два
или
Определение
индивидуального
вклада
коморбидных
факторов
прогрессирования
тяжелые
формы
важно,
так
предотвращение
осложнений
неблагоприятных
событий
зависит
лежащих
их
механизмов
влияния
течение
В
этом
обзоре
мы
представляем
существующую
информацию
о
влиянии
основных
Early
in
the
pandemic,
impact
of
comorbidities
on
severity
and
outcomes
was
noted.
Since
then,
much
attention
has
focused
comorbidity
issues
associatedwith
SARS-CoV-2
infection
long-term
consequences
Chronic
diseases
that
disrupt
body’s
homeostasis
make
patients
more
prone
to
infections.
Having
chronic
isassociated
with
higher
a
risk
death
from
In
addition
respiratory
complications,
is
associated
an
increased
cardiovascularevents
such
as
heart
attacks,
myocardial
infarctions,
strokes
thrombosis.
Patients
pre-existing
hypertension,
cardiovascular
disease,
diabetes,
obesity
are
particularly
susceptible
these
complications.
The
most
common
comorbid
infected
SARSCoV-
2
coronavirus
affect
development
prognosis
metabolic
disorders
syndrome,
obesity,
hyperlipidemia
well
hypertension
diseases.
pathophysiological
mechanisms
have
infection.
virus
capable
directly
damaging
vascular
endothelium
inducing
systemic
inflammatory
response
prothrombotic
state
aggravate
Many
patients,
especially
older
history
two
or
identifying
individual
contribution
factors
progression
severe
forms
important,
since
prevention
complications
adverse
events
depends
underlying
influence
course
this
review,
we
present
existing
information
major
Язык: Русский
Associations between pre-existing comorbidities and in-hospital cardiovascular events and mortality among COVID-19 patients in Bangladesh: a secondary analysis of a prospective cohort study
BMJ Open,
Год журнала:
2024,
Номер
14(8), С. e083982 - e083982
Опубликована: Авг. 1, 2024
Objective
To
identify
the
associations
of
in-hospital
cardiovascular
events
and
mortality
with
pre-existing
comorbidities
disease
(CVD)
risk
factors
among
COVID-19
patients
in
Bangladesh
without
vaccine
availability.
Design
A
secondary
analysis
a
prospective
multicountry
study.
Setting
Three
COVID-19-designated
hospitals
Bangladesh.
Participants
Adult
aged
≥18
years
PCR-positive
admitted
between
10
October
2020
31
July
2021
at
participating
hospitals.
Outcome
measures
In-hospital
mortality.
Main
exposures
Pre-existing
factors.
Results
In
897
patients,
18.7%
developed
12.6%
died.
After
adjusting
for
clinical
information
treatment,
two
(excluding
CVD
factors)
were
significantly
associated
(adjusted
(adj.)
OR
2.47,
95%
CI
1.24
to
4.90).
Patients
higher
heart
rate
admission
(adj.
1.03,
1.01
1.04)
those
who
receiving
intravenous
fluids
2.13,
1.23
3.70)
or
antibiotics
4.54,
1.47
14.01)
had
odds
events.
The
lower
antiviral
medications
0.31,
0.18
0.53).
There
no
interactions
other
covariates
models.
Comorbidities
not
30-day
Cox
regression
models
after
treatment.
within
30
days
was
corticosteroids
HR
2.82,
1.48
5.38)
treatment
0.53,
0.34
0.81).
Those
having
increased
hazard.
Conclusions
Clinical
affected
events,
which
subsequently
patients.
regardless
require
close
monitoring
Язык: Английский
ВИВЧЕННЯ ВПЛИВУ КОРОНАВІРУСНОЇ ХВОРОБИ НА РЕПРОДУКТИВНЕ ЗДОРОВ'Я ЧОЛОВІКІВ
Deleted Journal,
Год журнала:
2024,
Номер
4 (04), С. 100 - 106
Опубликована: Дек. 30, 2024
Ключовою
проблемою
системи
охорони
здоров’я
залишається
відсутність
ефективного
та
безпечного
методу
лікування
SARS
CoV-2,
багато
нез’ясованих
питань
патогенезу
цього
захворювання.
Вивчення
ролі
рецепторів
ангіотензин
перетворювального
ферменту
другого
типу,
цитокінового
шторму,
дисфункції
клітин
ендотелію
з
розвитком
гемолітичного
мікротромбоваскуліту
як
патогенетичного
ланцюгу
COVID-19
використовується
для
розробки
таргентної
ад’ювантної
терапії.
Але
ще
не
до
кінця
з’ясованим
вплив
вірусу
CoV-2
на
різні
органи
і
системи,
особливо
при
наявності
коморбідної
патології.
До
теперішнього
часу
недостатньо
вивчено
перебіг
запального
процесу
в
чоловіків
хронічним
запаленням
урогенітального
тракту.
На
сьогоднішній
день
наші
знання
про
чоловічу
репродуктивну
систему
вказують
її
крихкість,
є
значні
зареєстровані
докази
того,
що
чоловіча
репродуктивна
система
вразлива
вірусних
інфекцій.
Порівняно
зі
здоровими
чоловіками
без
Covid-19,
ряд
дослідників
виявили
значне
збільшення
запалення
окислювального
стресу
клітинах
сперми
Covid-19.
Цей
вірус
також
негативно
вплинув
концентрацію,
рухливість
форму
сперматозоїдів.
Нашим
дослідженням
встановлено,
шо
у
хворих
наявністю
хронічних
інфекційних
процесів
урогенітальному
тракті
відмічаються
зміни
профілю
сироватці
–
концентрація
ряду
цитокінів
зазнає
змін,
а
інших
межах
нормативних
величин,
саме:
зниження
концентрацій
ММР-2,
хемокінів
фракталкіну
RANTES,
різке
показників
IL-8,
МСР-1.
Тривалий
запальний
процес
статевих
органах
супроводжується
виснаженням
локальної
імунної
наслідком
чого
розвиток
інфертильності.
Перенесена
інфекція
впливає
суттєвим
чином
рівні
спермі
із
Підвищення
вмісту
патологічних
форм
сперматозоїдів
частини
пацієнтів,
які
перенесли
коронавірусну
інфекцію
пояснюється
можливим
впливом
сперматогенез
неімунних
факторів
(гіпертермія,
медикаментозне
тощо).
Novel polymer-based hydrogels of recent research in drug delivery for disease treatment related to SARS-CoV-2 virus
eXPRESS Polymer Letters,
Год журнала:
2023,
Номер
18(2), С. 160 - 192
Опубликована: Дек. 6, 2023
Polymer-based
hydrogels
are
hydrophilic
polymer
networks
with
a
remarkable
capacity
to
absorb
substantial
amounts
of
water
and
biological
fluids,
rendering
them
highly
attractive
for
drug
delivery
applications.The
COVID-19
pandemic
has
acted
as
catalyst
research
innovation
in
the
realm
polymer-based
delivery,
particular
emphasis
on
antiviral
therapeutics,
vaccines,
diagnostics,
precision
respiratory
system.The
distinctive
attributes
hydrogels,
such
their
biocompatibility,
customizable
release
profiles,
ease
functionalization,
establish
versatile
platforms
development
advanced
systems
combat
not
only
but
also
spectrum
other
infectious
diseases.This
study
is
dedicated
scruti-nizing
evaluating
characteristics
employed
treatment
diseases
associated
SARS-CoV-2
virus.Furthermore,
investigation
introduces
novel
classification
system
deployed
SARS-CoV-2-related
diseases.Additionally,
paper
provides
an
up-to-date
evaluation
latest
developed
utilized
dis-eases
linked
virus,
based
conducted
through
recent
months
2023.
Язык: Английский
Evaluating male sexual function and reproductive health during Omicron outbreak in China: A cross-sectional study
Authorea (Authorea),
Год журнала:
2023,
Номер
unknown
Опубликована: Май 27, 2023
Our
aim
was
to
estimate
changes
in
sexual
function
and
semen
quality
men
recovering
from
infection
since
the
Omicron
pandemic
started
China
late
2022.
We
collected
1540
questionnaires
assessed
male
before
acute
phase
after
by
using
International
Index
of
Erectile
Function-5,
Premature
Ejaculation
Diagnostic
Tool,
Arizona
Sexual
Experience
Scale.
also
analysis
results
247
patients.
During
infection,
proportion
erectile
dysfunction
significantly
higher
than
but
ejaculatory
not
altered；
In
addition,
showed
significant
difference
concentration,
activity
PR
a+b
sperm
forward
movement
compared
pre-infection.
can
affect
as
well
experience
patients
phase.
The
risk
factors
for
decreased
due
included
body
temperature
anxiety
during
infection.
Язык: Английский