Note: Descriptions are shown in the official language in which they were submitted.
COMPOSITION FOR PREVENTING OR TREATING COVID-19, INCLUDING GOLD
NANOPARTICLE AS ACTIVE INGREDIENT
TECHNICAL FIELD
The present invention relates to a composition for preventing or treating
coronavirus
infection, comprising a gold nanoparticle as an active ingredient.
BACKGROUND OF THE INVENTION
Coronavirus disease (COVID-19) is an infectious disease caused by a newly
discovered
coronavirus. Most people infected with the COVID-19 virus will experience mild
to moderate
respiratory illness. Coronavirus infection mainly results in a respiratory
infection that has
spread worldwide since it recently occurred in Wuhan, China in December 2019.
As shown in FIG. 1, coronavirus includes a spike protein, and a spike
glycoprotein of
coronavirus-19 mediates viral entry and membrane fusion to host cells, and
thus has become a
main target for vaccines and therapeutic products (Artificial Cells, Blood
Substitutes, and
Biotechnology, vol 40. pp 75-96). However, so far, it was confirmed that most
monoclonal
antibodies (mAbs) do not neutralize synonymous mutations.
The spike glycoprotein of the coronavirus has a multifunctional molecular
structure
mediating coronavirus entry into host cells. As shown in FIG. 2, first, the
spike glycoprotein
binds to a receptor on the host cell surface via an Si subunit. Two domains of
Si in other
coronaviruses are known to induce viral attachment by recognition of various
host receptors.
Such a spike protein is present in the form of two structurally distinct pre-
fusion and post-fusion
morphologies.
The present invention is provided to solve the above-described problems, and
the
inventors demonstrated that a gold nanoparticle hinders the morphological
change of corona
virus, and is capable of blocking entry into a cell.
However, technical problems to be solved in the present invention are not
limited to the
above-described problems, and other problems which are not described herein
will be fully
understood by those of ordinary skill in the art from the following
descriptions.
SUMMARY OF THE INVENTION
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The present invention provides a pharmaceutical composition for treating or
preventing
COVID-19, comprising a gold nanoparticle.
In addition, the present invention provides a method of treating or preventing
coronavirus
COVID-19, comprising administering a composition containing a gold
nanoparticle to a subject.
Furthermore, the present invention provides a use of a composition including a
gold
nanoparticle for treating or preventing COVID-19.
In one embodiment of the present invention, the gold nanoparticle hinders the
morphological change of a coronavirus protein to block the entry of a
coronavirus protein into a
cell.
In another embodiment of the present invention, the gold nanoparticle is
included in the
form of a negatively-charged gold colloidal solution.
In still another embodiment of the present invention, the composition further
includes a
Si proteolysis inhibitor.
In yet another embodiment of the present invention, the composition is a
composition for
a nasal spray.
In yet another embodiment of the present invention, the gold nanoparticle has
a diameter
of 0.1 to 100 nm.
A composition according to the present invention contains a gold nanoparticle
as an
active ingredient, and in the present invention, an effect of treating and
preventing COVID-19
according to the treatment of the gold nanoparticle was confirmed. The gold
nanoparticle
hinders the morphological change of a coronavirus protein, so that the entry
of the coronavirus
protein into a cell can be blocked, resulting in the prevention or treatment
of COVID-19.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 schematically shows the morphology of coronavirus.
FIG. 2 shows structures before and after fusion due to entry of the
coronavirus into a viral
host cell.
FIG. 3 shows a gold nanoparticle applied to the coronavirus.
FIG. 4 shows that a gold nanoparticle is added to disulfide bonding between
spike
proteins of the coronavirus.
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FIG. 5 schematically shows a process of treating a coronavirus disease using a
composition of the present invention binding to the virus.
FIG. 6 shows the morphology of an Si proteolysis inhibitor-binding gold
nanoparticle.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides that a gold nanoparticle hinders a
morphological change
of a coronavirus protein, to block the entry of a coronavirus protein into a
cell, resulting in
inhibition of the cellular entry of the coronavirus.
The present invention also provides a pharmaceutical composition for treating
or
preventing COVID-19, comprising a gold nanoparticle.
As shown in FIG. 3, the gold nanoparticle hinders the morphological change in
a
coronavirus protein to block the entry of the coronavirus protein into a cell.
According to such
blocking, COVID-19 may be treated or prevented. In further detail, as shown in
FIG. 4, a
negatively-charged colloidal gold solution may be inserted between a spike
protein and an
envelope protein. The insertion of the gold nanoparticle makes the
morphological change of
the spike protein difficult.
In the present invention, the gold nanoparticle may be provided in the form of
a
negatively-charged gold colloidal solution. When the gold colloidal solution
is used through
spraying into the nasal cavity, the viral entry into cells may be more
effectively prevented, but
there are no limitations on the administration method.
In the present invention, the gold nanoparticle has a diameter of 0.05 to 100
nm,
preferably 0.1 to 50 nm, more preferably 0.1 to 35 nm, and most preferably 0.1
to 10 nm.
The "coronavirus-19", which is a causative virus of a disease to be prevented
or treated
by the composition of the present invention, is a novel type of virus first
identified in Wuhan,
China in 2019, and the genomic and protein information associated with the
coronavrius-19 may
be freely collected from a research information database and used.
The term "prevention" used herein refers to all actions of suppressing COVID-
19 or
delaying the onset thereof by administration of the pharmaceutical composition
according to the
present invention.
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The term "treatment" used herein refers to all actions involved in alleviating
or
beneficially changing symptoms of COVID-19 by administration of the
pharmaceutical
composition according to the present invention.
The present invention provides the simplest method of blocking the entry of a
spike
protein into a cell by hindering the morphological change of the protein using
negatively-charged
colloidal gold entering from an endotracheal tube or a nasal sprayer to the
lungs. Here, small
amounts of gold particles may migrate into the systemic circulatory system (10
to 40 nm).
FIG. 5 shows that, when replicated coronavirus-19 is released from lung cells,
a
negatively-charged colloidal gold nanoparticle may easily bind to the
positively-charged
replicated virus, the virus may then be removed by phagocytosis, and thus the
progression of
infection may be prevented.
In addition, the gold nanoparticle of the present invention may be used in
combination
with an Si proteolysis inhibitor. As shown in FIG. 6, camostat, which is the
Si proteolysis
inhibitor, and the negatively-charged gold nanoparticles may be combined by
ionic bonding, and
therefore, the efficacy of the Si proteolysis inhibitor may increase. That is,
the progression of
infection caused by coronavirus-19 may be inhibited by bonding between the
gold nanoparticle
acting as a protein form blocker and the Si proteolysis inhibitor. The Si
proteolysis inhibitor
may be, as an example, camostat mesylate, but the present invention is not
limited thereto.
The gold colloidal solution provided in the present invention refers to a
colloidal solution
or suspension of submicrometer-sized gold nanoparticles, present in a fluid,
generally, water.
The pharmaceutical composition according to the present invention may include
a
pharmaceutically acceptable carrier in addition to the active ingredient.
Here, the
pharmaceutically acceptable carrier is commonly used in preparation, and
includes lactose,
dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, calcium phosphate,
alginate, gelatin,
calcium silicate, microcrystalline cellulose, polyvinyl pyrrolidone,
cellulose, water, syrup,
methyl cellulose, methylhydroxybenzoate, propyl hydroxybenzoate, talc,
magnesium stearate
and mineral oil, but the present invention is not limited thereto. In
addition, the pharmaceutical
composition according to the present invention may further include a
lubricant, a wetting agent, a
sweetening agent, a flavor, an emulsifier, a suspending agent or a
preservative, in addition to the
above-mentioned components.
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The pharmaceutical composition of the present invention may be orally or
parenterally
(e.g., intravenously, subcutaneously, intraperitoneally or locally)
administered by a desired
method, and a dosage may vary according to a patient's condition and weight,
the severity of a
disease, a dosage form, an administration route and duration, but may be
appropriately selected
by those of ordinary skill in the art.
The pharmaceutical composition of the present invention may be administered at
a
pharmaceutically effective amount. The "pharmaceutically effective amount"
used herein
refers to an amount sufficient for treating a disease at a reasonable
benefit/risk ratio applicable
for medical treatment, and an effective dosage may be determined by parameters
including a type
of a patient's disease, severity, drug activity, sensitivity to a drug,
administration time, an
administration route and an excretion rate, the duration of treatment and
drugs simultaneously
used, and other parameters well known in the medical field. The pharmaceutical
composition
of the present invention may be administered separately or in combination with
other therapeutic
agents, and may be sequentially or simultaneously administered with a
conventional therapeutic
agent, or administered in a single or multiple dose(s). In consideration of
all of the above-
mentioned parameters, it is important to achieve the maximum effect with the
minimum dose
without a side effect, and such a dose may be easily determined by one of
ordinary skill in the art.
Specifically, the effective amount of the pharmaceutical composition of the
present
invention may be dependent on a patient's age, sex, condition and body weight,
an absorption
rate of the active ingredient in the body, an inactivation rate, an excretion
rate, a type of disease,
or a drug used in combination, and may be generally administered at 10 to 1000
mg/kg,
preferably 50-750 mg/kg, most preferably 100 to 500 mg/kg of body weight daily
or every other
day, or divided into one or three doses. However, the effective amount may
vary depending on
an administration route, the severity of obesity, sex, body weight or age, and
therefore, the scope
.. of the present invention is not limited by the dose in any way.
In addition, the present invention provides a method of treating or preventing
coronavirus
infection or COVID-19, which includes administering a composition including a
gold
nanoparticle to a subject. The term "subject" used herein refers to a target
in need of treatment,
and more specifically, a mammal such as a human or a non-human primate, a
mouse, a rat, a dog,
a cat, a horse, or a cow.
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Furthermore, the present invention may provide a use of a composition
including a gold
nanoparticle to treat or prevent coronavirus infection or COVID-19.
Hereinafter, to help in understanding the present invention, an exemplary
example will be
suggested. However, the following example is merely provided to more easily
understand the
present invention, and not to limit the present invention.
EXAMPLES
To confirm the effect of the composition of the present invention, a
composition
including 2-nm gold particles was prepared. The effect of the composition
including the gold
nanoparticle was studied by intratracheal administration to an adult female
mouse. As a result,
1 hour after the single administration, the administered gold nanoparticles
were found in lung
macrophages.
From the above result, it can be confirmed that the inert gold nanoparticles
administered
into the trachea are involved in phagocytosis mediated by lung macrophages.
That is, a negatively-charged colloidal gold solution may approach coronavirus
which has
positively-charged porosity and hinders the morphological change of Si and S2
domains by
covalent binding to a cysteine residue of a spike protein, demonstrating that
coronavirus-19
particles that are not able to be fused to lung cells through viral attachment
to a host receptor are
likely to be phagocytosed by lung macrophages.
It should be understood by those of ordinary skill in the art that the above
description of
the present invention is exemplary, and the exemplary embodiments disclosed
herein can be
easily modified into other specific forms without departing from the technical
spirit or essential
features of the present invention.
Therefore, the exemplary embodiments described above should be interpreted as
illustrative and not limited in any aspect.
Industrial Applicability
The composition of the present invention is a pharmaceutical composition for
treating or
preventing coronavirus disease-19 (COVID-19), including a gold nanoparticle,
and may block
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Date Recue/Received Date 2020-07-14
the entry of a coronavirus protein into a cell by hindering the morphological
change of the spike
protein of the coronavirus when the gold nanoparticles are administered.
Therefore, the
composition may be effectively used in the field of treating a novel
infectious disease, such as
C OVID- 1 9.
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