Journal
Identification
=
PEP
Article
Identification
=
68388
Date:
July
8,
2011
Time:
3:21
pm
Peptides
32
(2011)
1518–1525
Contents
lists
available
at
ScienceDirect
Peptides
j
our
na
l
ho
me
p
age
:
www.elsevier.com/locate/peptides
Virucidal
activity
of
a
scorpion
venom
peptide
variant
mucroporin-M1
against
measles,
SARS-CoV
and
influenza
H5N1
viruses
Qiaoli
Li
b,1
,
Zhenhuan
Zhao
a,1
,
Dihan
Zhou
b
,
Yaoqing
Chen
a,b
,
Wei
Hong
a
,
Luyang
Cao
a
,
Jingyi
Yang
b
,
Yan
Zhang
b
,
Wei
Shi
b
,
Zhijian
Cao
a
,
Yingliang
Wu
a
,
Huimin
Yan
a,b,∗
,
Wenxin
Li
a,∗∗
a
State
Key
Laboratory
of
Virology,
College
of
Life
Sciences,
Wuhan
University,
Wuhan
430072,
People’s
Republic
of
China
b
State
Key
Laboratory
of
Virology,
Wuhan
Institute
of
Virology,
Chinese
Academy
of
Sciences,
Wuhan
430071,
People’s
Republic
of
China
a
r
t
i
c
l
e
i
n
f
o
Article
history:
Received
16
April
2011
Received
in
revised
form
12
May
2011
Accepted
12
May
2011
Available
online
19
May
2011
Keywords:
Mucroporin-M1
Scorpion
venom
Measles
SARS-CoV
H5N1
Antiviral
a
b
s
t
r
a
c
t
Outbreaks
of
SARS-CoV,
influenza
A
(H5N1,
H1N1)
and
measles
viruses
in
recent
years
have
raised
seri-
ous
concerns
about
the
measures
available
to
control
emerging
and
re-emerging
infectious
viral
diseases.
Effective
antiviral
agents
are
lacking
that
specifically
target
RNA
viruses
such
as
measles,
SARS-CoV
and
influenza
H5N1
viruses,
and
available
vaccinations
have
demonstrated
variable
efficacy.
Therefore,
the
development
of
novel
antiviral
agents
is
needed
to
close
the
vaccination
gap
and
silence
outbreaks.
We
previously
indentified
mucroporin,
a
cationic
host
defense
peptide
from
scorpion
venom,
which
can
effectively
inhibit
standard
bacteria.
The
optimized
mucroporin-M1
can
inhibit
gram-positive
bac-
teria
at
low
concentrations
and
antibiotic-resistant
pathogens.
In
this
investigation,
we
further
tested
mucroporin
and
the
optimized
mucroporin-M1
for
their
antiviral
activity.
Surprisingly,
we
found
that
the
antiviral
activities
of
mucroporin-M1
against
measles,
SARS-CoV
and
influenza
H5N1
viruses
were
notably
increased
with
an
EC
50
of
7.15
g/ml
(3.52
M)
and
a
CC
50
of
70.46
g/ml
(34.70
M)
against
measles
virus,
an
EC
50
of
14.46
g/ml
(7.12
M)
against
SARS-CoV
and
an
EC
50
of
2.10
g/ml
(1.03
M)
against
H5N1,
while
the
original
peptide
mucroporin
showed
no
antiviral
activity
against
any
of
these
three
viruses.
The
inhibition
model
could
be
via
a
direct
interaction
with
the
virus
envelope,
thereby
decreasing
the
infectivity
of
virus.
This
report
provides
evidence
that
host
defense
peptides
from
scor-
pion
venom
can
be
modified
for
antiviral
activity
by
rational
design
and
represents
a
practical
approach
for
developing
broad-spectrum
antiviral
agents,
especially
against
RNA
viruses.
©
2011
Elsevier
Inc.
All
rights
reserved.
1.
Introduction
Rapidly
changing
global
landscapes
and
local
environments,
enormous
increases
in
the
human
population
and
urbanization
in
many
developing
countries,
and
the
advances
in
the
speed
and
volume
of
global
transportation
have
created
increased
oppor-
tunities
for
the
emergence
and
re-emergence
of
viral
diseases.
Viruses
with
RNA
as
their
genetic
material
can
quickly
adapt
to
and
exploit
these
various
conditions
because
of
their
high
genetic
variation
rates
(mutation,
recombination
and
reassortment).
Not
surprisingly,
many
prominent
recent
examples
of
emerging
or
re-emerging
diseases
have
been
caused
by
RNA
viruses,
such
as
SARS-Coronavirus,
H5N1
avian
influenza
viruses,
H1N1,
HIV,
Han-
∗
Corresponding
author
at:
Mucosal
Immunity
Research
Group,
State
Key
Labora-
tory
of
Virology,
Wuhan
Institute
of
Virology,
Chinese
Academy
of
Sciences,
Wuhan
430071,
People’s
Republic
of
China.
Tel.:
+86
27
87197103;
fax:
+86
27
87197103.
∗∗
Corresponding
author.
Tel.:
+86
27
68752831;
fax:
+86
27
68756746.
E-mail
addresses:
hmyan@wh.iov.cn
(H.
Yan),
liwxlab@whu.edu.cn
(W.
Li).
1
These
authors
contributed
equally
to
the
work.
tavirus,
and
West
Nile
virus
[10–12,15,21,23,32].
Outbreaks
of
measles
continue,
and
it
is
still
the
leading
cause
of
morbidity
and
mortality
in
children
worldwide,
despite
the
availability
of
live
attenuated
vaccines
for
more
than
30
years
[2,6].
Effective
antiviral
agents
are
lacking
that
specifically
target
RNA
viruses
such
as
measles,
SARS-CoV
and
influenza
H5N1.
The
current
available
therapies
used
in
the
clinic
for
measles
virus
infection
treatment,
which
is
administered
orally
or
intravenously
alone
or
in
combi-
nation
with
immune
serum
globulin,
have
demonstrated
variable
efficacies
and
side
effects
such
as
high
teratogenicity
and
ane-
mia
[2,30,31].
Many
other
strategies,
such
as
antisense
molecules,
adenosine
and
guanosine
nucleosides,
brassinosteroids,
coumarins,
peptide
inhibitors,
and
modulators
of
cholesterol
synthesis,
have
also
failed
[2,25,26].
Moreover,
approved
or
universally
recom-
mended
therapies
have
been
lacking
for
SARS-CoV
and
influenza
H5N1
infections
until
now,
even
though
more
and
more
antiviral
agents
against
SARS-CoV
and
influenza
H5N1
have
been
reported
[8,17,24].
Therefore,
the
development
of
new
antiviral
agents
is
needed
to
provide
more
options
for
managing
cases
of
diseases
caused
by
RNA
viruses
in
both
developed
and
developing
coun-
tries.
0196-9781/$
–
see
front
matter
©
2011
Elsevier
Inc.
All
rights
reserved.
doi:10.1016/j.peptides.2011.05.015