CN111686253A

CN111686253A - A new method for preventing and killing coronavirus

Info

Publication number: CN111686253A
Application number: CN202010104617.3A
Authority: CN
Inventors: 田中民; 刘马宝; 栾龙
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-02-20
Filing date: 2020-02-20
Publication date: 2020-09-22

Abstract

The invention designs atomized charged particles to change the charge characteristics or geometric configuration of the virus or the cell surface of a receptor according to the physical characteristics of the pathogenic mechanism of the coronavirus, namely the charge characteristics and the geometric shape of the combination of protein and protein, thereby blocking the pathogenic process of the coronavirus and not aiming at killing the virus in a body. To date, there is no drug or method that can destroy or kill viruses directly in the body, except by the immune mechanisms of the virus itself. However, reducing the copy number of the virus or interrupting the infection process of the virus to human bodies is an effective method for resisting virus at present.

Description

A new method for preventing and killing coronavirus

Technical Field

The invention relates to the field of virus treatment methods, in particular to a novel method for preventing and killing coronavirus.

Background

Coronaviruses are positive strand single stranded RNA viruses with a mantle, which can infect humans, mice, pigs, cats, dogs, wolves, chickens, cattle, avian vertebrates. The coronaviruses discovered so far are animal coronaviruses such as avian Infectious Bronchitis (IB), porcine Transmissible Gastroenteritis (TGE), Porcine Epidemic Diarrhea (PED), Porcine Hemagglutinating Encephalomyelitis (PHE), newborn calf diarrhea (BC), Foal Gastroenteritis (FGE), Feline Infectious Peritonitis (FIP), feline enteric coronavirus diseases (FEC), etc., and the human-infecting coronaviruses are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV and MERS-CoV, 2019 novel coronaviruses (2019-nCoV) which are the 7 th known coronaviruses that can infect humans.

Coronaviruses bind to receptors on host cells through their surface glycoproteins, and then enter the cell by fusion of the viral envelope with the cell membrane. Coronavirus invades from the respiratory tract or intestinal tract, reproductively proliferates in the respiratory tract or intestinal tract mucosal epithelial cells, and causes viremia, and then spreads to various tissues and organs, particularly to the lung, spleen and lymphoid tissues. Acute lung lesions are mainly characterized by massive exudation of interstitial macrophages and lymphocytes of the lung, leading to pulmonary edema and lung consolidation and formation of hyaline membrane lesions, leading to Acute Respiratory Distress Syndrome (ARDS), and pulmonary fibrosis occurs after three weeks of onset. Coronaviruses thus cause mainly severe lung lesions, accompanied by systemic diseases of the immune system, and death of the patient results from multiple organ failure.

Coronavirus is transmitted by respiratory droplets, aerosols and direct or indirect contact at close distances, so that the coronavirus is rapidly transmitted in the global range along with the extension of vehicles.

Pathogenesis of coronavirus

The S protein of coronavirus is composed of 1160-1400 amino acids and contains 21-35N-glycosylation sites. The S protein forms a special corolla structure on the surface of the virus in the form of trimer. The S protein is split into two parts, S1 and S2, under the action of host cell protease, S1 mainly functions to bind with host cell surface receptors, and S2 subunit mediates virus-cell and cell-cell membrane fusion. The cleavage of the S protein plays a critical role in the invasion capacity and virulence of the virus.

The cleavage of S protein can be roughly divided into two cases, i.e., S protein is cleaved during virus assembly

The process occurs in the Golgi apparatus of the host cell. The other is that S protein is split when the virus is infected, namely S protein is not split in the virus assembly process, and the splitting and activation of S protein depend on proteases on the surface of host cells during infection. 2019-nCoV coronavirus belongs to the second cleavage mode, and S protein needs to be combined with ACE2 receptor to cause the S protein to be changed in conformation before being cleaved by Cathepsin L (Cathepsin L, CPL) or other proteases in cells. The virus activated by the S protein can enter a host cell in a membrane fusion mode. SARS-CoV virus requires both acidic and protease co-induction to complete membrane fusion. Early infection of SARS-CoV virus stimulates secretion of elastase (or trypsin-E) from lung epithelial cells of patients, and SARS-CoV can directly enter host cells under the action of this protease. Recent studies suggest that coronaviruses should bind to endosomes by utilizing Clathrin (Clathrin) -mediated cellular endocytosis, and that different viruses differ in whether the S protein is cleaved in early endosomes or in lysosomes, during invasion of target cells. The N terminal S1-NTD of the S protein after cleavage is generally combined with host carbohydrate receptors, and the C terminal S1-CTD is combined with protein receptors. The present study shows that, besides coronavirus, the main viral domains of 3 genera can recognize at least 2 polysaccharide receptors and 5 protein receptors, and present a complex multi-receptor binding pattern.

At least 5 kinds of protein receptors of coronavirus are currently found, for example, CEACAM1 is a receptor of MHV virus and is the first found protein receptor; the APN receptor is a type II transmembrane protein expressed on the top of respiratory and intestinal epithelial cells, and HCoV-229E, TGEV, feline coronavirus type II and CCoV all use APN of respective hosts as a receptor. DPP4 was found to be a receptor for MERS-CoV. SARS-CoV, IBV and FCoV viruses have as receptors the calcium-dependent lectins of host cells. ACE2 is a newly discovered metalloprotease behind 2003 your Sars, belonging to the type I transmembrane glycoprotein, with carboxypeptidase activity. The extracellular domain of human ACE2 consists of 2 subunits, of which the zinc metallopeptidase domain can be further divided into 2 subdomains (I and II) forming a long and deep cleft, with the ridges around the top of the cleft carrying very high negative charges which interact with the positive charges of the RBD on the S protein, allowing ACE2 to bind to the S protein. In addition, ACE2 has a promoting effect on the replication of SARS-CoV. The receptor for HCoV-NL63 is also ACE 2; comparing the binding sites of RBD of both SARS-CoV and HCoV-NL63 with ACE2, it was found that the RBD of both viruses surrounds the K353 residue of ACE2, indicating that both SARS-CoV and HCoV-NL63 tend to bind to the same specific region of the receptor protein.

Sialic acid and heparin sulfate are also commonly used polysaccharide receptors for coronaviruses. Heparin sulfate belongs to a linear polysaccharide substance containing sulfate groups, and is usually located on the cell surface to be combined with extracellular matrix protein to form glycoprotein with negative charge. The S protein of the alphacoronavirus FIPV binds to heparin sulfate into the cell. Sialonic acid, also known as N-acetylneuraminic acid, is another natural carbohydrate widely present in biological systems, sialic acid carries a very strong negative charge, usually located at the end of a glycoprotein or glycolipid on the surface of the cell membrane. The beta coronavirus S protein has a salivary acid binding property, particularly BCV and HCoV-OC 43. Thus, coronaviruses usually bind to the positive charge of the RBD domain on the S protein and to regions of the invading cell surface that carry a strong negative charge, such as the ACE2 zinc metallopeptidase region or the strongly negatively charged group region of sialic acid and heparin sulfate. S protein is cracked by proteolytic enzyme on the surface of the infected cell or in the cell, and the endocytosis of the virus particles is obtained by depending on an acidic microenvironment on the surface of the infected cell, so that the virus particles enter the infected cell.

Disclosure of Invention

It is an object of embodiments of the present invention to provide a novel method for preventing and killing coronaviruses, so as to prevent and kill coronaviruses. The specific technical scheme is as follows:

the embodiment of the invention provides a novel method for preventing and killing coronavirus, which comprises the following steps:

selecting and obtaining substances or compounds for reducing the activity of coronavirus according to the principle of surface negative charge characteristics; wherein the substance or compound has the property of having a negative surface charge characteristic or binding to a positive surface charge of a coronavirus, said substance or compound binding to the s-protein receptor of said coronavirus to inactivate the virus;

the substance capable of reducing the virus activity has definite surface negative charge characteristics of the substance; is easy to combine with coronary virus.

Alternatively, typical biochemical substances with surface negative charge properties that can achieve coronavirus inactivation are heparin sulfate or sialic acids.

Alternatively, the active substance may be micronized and caused to act by active inhalation using nebulized particles of a solution of the substance or compound capable of inactivating coronavirus which is caused to act by active inhalation when the human or animal breathes.

Optionally, physically atomizing the substance or compound using an ultrasonic device; when the liquid is used, a preset physical mode is adopted to realize the micronization of the liquid.

Alternatively, the material or compound with potential surface negative charge characteristic can be enhanced physically, which involves a special atomizer device, an electrostatic field applying device combined with piezoelectric ultrasonic vibrator can generate ionization atomization function and make the material or compound with stronger surface negative charge.

Alternatively, an electrostatic field applying apparatus combined with a piezoelectric ultrasonic vibrator is characterized in that a medicinal liquid is atomized and negatively charged through a set of coaxial or non-coaxial parallel channels.

Optionally, the negatively charged amino acids aspartic acid (Asp) and glutamic acid (Glu) are amino acids with excess carboxyl groups, which dissociate hydrogen protons in an alkaline aqueous solution to form negatively charged amino acid radical ions, and can form negatively charged atomized droplets in an electrospray ionization process or an ultrasonic atomization process.

Optionally, the defensin is a kind of disulfide-bond-rich cationic polypeptide, and is an antibacterial peptide with direct bactericidal function generated in the biological evolution process. Can also be used as a substance for preventing virus invasion. The method is characterized in that: the positive charge of the self-body blocks a region with strong negative charge, such as the strong negative charge structural domain of ACE2 protein, thereby forming a competitive binding recognition site with coronavirus, and further reducing the infection probability of the virus.

Optionally, some substances and compounds in the aqueous or alcoholic extract of glycyrrhiza uralensis of Chinese medicinal materials also have the effect of inactivating coronavirus by enhancing the surface negative charge characteristics.

The invention designs atomized charged particles to change the charge characteristics or the geometric configuration of the virus or the cell surface of a receptor according to the physical characteristics of the pathogenic mechanism of the coronavirus, namely the charge characteristics and the geometric shape of the combination of protein and protein, thereby blocking the pathogenic process of the coronavirus, and not aiming at killing the virus in organisms. To date, there is no drug or method that can destroy or kill viruses directly in the body, except by the immune mechanisms of the virus itself. However, reducing the copy number of the virus or interrupting the infection process of the virus to human bodies is an effective method for resisting virus at present.

The design and anti-coronavirus idea provided by the invention is a brand-new technical idea for inactivating coronavirus, which is not provided in China and China. The traditional medicine research and development aiming at the virus has not made breakthrough progress so far, including AIDS virus, hepatitis B virus in China, supporting therapy and improving autoimmunity are still the main strategies for antiviral treatment.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below.

FIG. 1 is a schematic diagram of a novel method for preventing and killing coronavirus according to an embodiment of the present invention;

FIG. 2 is a schematic diagram of an atomizer apparatus according to an embodiment of the present invention;

FIG. 3 is a schematic diagram of another atomizer apparatus provided in accordance with an embodiment of the present invention;

fig. 4 is a schematic diagram of another atomizer apparatus according to an embodiment of the present invention.

Detailed Description

The technical solution in the embodiment of the present invention will be described below with reference to the drawings in the embodiment of the present invention.

Example 1

First, a new method for preventing and killing coronary viruses provided by the embodiment of the present invention is described with reference to fig. 1 and 2.

The idea proposed by the invention is as follows:

1. the present invention designs physical treatment method based on the biophysical characteristics of virus pathogenic biological mechanism, and finds out the virus inactivating and attenuating mode based on the virus and charge characteristics. And will be effective against all viruses that have the S protein as the entry point.

2. The target is to block infection of the virus in vivo, but not to kill and destroy the virus in vivo. Because the virus is killed in vivo, the product also has great harm to human body. Therefore, the aerosol therapy design firstly considers the biological safety, does not damage the human body and reduces the immunity of the human body.

3. Coronavirus which can not infect human body is discharged out of the body along with the exhaled air. On one hand, the human body is free from the infection of the virus, and on the other hand, the exhaled virus can be subjected to strong physical and chemical killing in vitro. The virus is led out and killed.

4. The equipment can also be used for preventive kill in public personnel-intensive environments. First, the charged atomizing gas is safe and can be continuously released in a common area. Viruses exhaled by the patient are trapped by the negatively charged aerosolized particles, reducing infectivity. Is killed by strong physical and chemical methods in a gas recovery device.

The design and anti-coronavirus thought proposed by the invention is a brand new research subject which is not proposed in the world and the China. The traditional medicine research and development aiming at the virus has not made breakthrough progress so far, and the AIDS virus, hepatitis B virus in China, supportive therapy and improvement of autoimmunity are still main strategies for antiviral treatment.

As shown in fig. 1 to 4, the method for preventing and eliminating coronavirus provided by the embodiment of the present invention specifically is that (1) according to the pathogenesis of coronavirus, the infection process of coronavirus is a complex biological process including cell recognition, enzymatic cleavage, endocytosis, plasma membrane fusion, etc., and any physical, chemical or biological method capable of interrupting or blocking the process will block the infection process of coronavirus, thereby obtaining the effect of anti-coronavirus.

(2) In the infection process of coronavirus, the virus needs to identify strong negative electricity regions on the surface of infected cells depending on the positive charge characteristics and geometric morphology of the coronavirus protein on the surface, so that the identification between the virus and the cells can be realized, and the next invasion process can be started. Therefore, the virus cannot be mutually identified with the infected cell by changing the charge characteristic and the geometric shape of the surface of the coronavirus or covering the charge characteristic and the geometric shape of the surface of the host cell, so that the antiviral effect is achieved.

(3) The drug is atomized into tiny particles with negative charges, a patient inhales the lung and the coronavirus through breathing to directly act, and the atomized particles with strong negative charges are combined with virus particles and combined with a positive charge structure domain on the surface of S protein, so that the recognition capability of the virus and cells is greatly reduced. Or nebulizing a positively charged molecule or compound for inhalation into the lung to block the strongly negatively charged domain on the surface of the renal epithelial cells, thereby blocking the binding of the coronavirus to the host cell. Belonging to the competitive inhibition of the activity of the virus.

(4) To achieve this, we have designed an atomising device as shown in the following figures. In the figure, a is the medicinal liquid needing atomization or already atomized; b is a group of parallel metal electrode pipelines which are provided with negative voltage, thereby forming a certain negative electric field. Such a device causes the liquid being ultrasonically atomized through its tube to be more negatively charged during the synergistic action of the ionization atomization.

(5) In order to strengthen the negative charge environment of atomized liquid, a repulsion negative electrode is additionally designed outside the atomizing spray head, and the atomized liquid is more released to the outside.

The invention designs two atomization modes to achieve high-efficiency, quick and fine atomization particle atomization equipment. The ultrasonic atomization is that piezoelectric ceramic is used for generating electronic high-frequency oscillation with oscillation frequency of 1.7MHz or 2.4MHz and no harm to human bodies and animals beyond the hearing range of human beings, so that the surface of a liquid is raised, cavitation is generated around the raised liquid surface, the liquid is atomized into small-particle aerial fog, and natural and elegant water mist is generated without heating or adding any chemical reagent. During the atomization process, a large number of negative ions, particularly negative oxygen ions, are also released, which are able to interact with the virus surface. (2) Electrospray ionization atomization. Electrospray ionization is believed to be the formation of finely charged droplets of liquid from a solution at the exit end of an electrospray needle under the action of a high electric field gradient and a sheath gas, the charge density on the surface of the droplets increasing as the solvent in the droplets evaporates. When the charge density increases to the Rayleigh stability limit, the droplets are electrostatically repelled and break up into smaller droplets, known as a coulomb explosion. In this droplet division process, the charge is distributed unequally until fine charged particles are formed. The concentration of highly volatile ions in the sample is higher at the surface of the droplet. When the electrostatic repulsive force between ions is large to some extent, ions with high volatility are preferentially ejected from the surface of the liquid droplet into the gas phase, and its counter ions remain in the liquid droplet and finally become a solid residue.

The ultrasonic atomization equipment and the principle are simple, and the cost is low, so that the test equipment is the first choice of the test equipment. Electrospray ionization atomization has the advantage of producing smaller, more finely atomized particles. The present atomisation device is therefore a device which combines the usual co-action with physical ultrasonic atomisation and ionisation atomisation.

Example 2

As shown in fig. 3, the atomization device of the present invention is used as a core component, and a power supply portion, a control device and a container for containing a medicinal liquid are combined to form an atomized medicinal releaser, so that the atomization and the outward spraying of the medicinal liquid are realized after the power supply is turned on. The atomized medicine particles are released in the open space, and the human and animals naturally inhale the medicine particles into the human and animal bodies in the breathing process, so that the effect of killing viruses is achieved.

Example 3

As shown in fig. 4, the aerosolization apparatus of the present invention communicates directly into the medical oxygen mask via a manifold, allowing the patient to inhale directly under pressure, with metering and timing assistance. Achieving the purpose of treatment.

It is noted that, herein, relational terms such as first and second, and the like may be used solely to distinguish one entity or action from another entity or action without necessarily requiring or implying any actual such relationship or order between such entities or actions. Also, the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such process, method, article, or apparatus. Without further limitation, an element defined by the phrase "comprising an … …" does not exclude the presence of other identical elements in a process, method, article, or apparatus that comprises the element.

The above description is only for the preferred embodiment of the present invention, and is not intended to limit the scope of the present invention. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present invention are included in the scope of protection of the present invention.

Claims

1. A novel method for preventing and killing coronavirus,

selecting and obtaining substances or compounds for reducing coronavirus activity according to surface negative charge characteristics of the substances; wherein the substance or compound has the property of having a negative surface charge characteristic or binding to a positive surface charge of a coronavirus, said substance or compound binding to the s-protein receptor of said coronavirus to inactivate the virus;

the substance capable of reducing the virus activity has definite surface negative charge characteristics of the substance; is easy to combine with the surface S protein receptor of coronavirus.

2. A novel method for the prophylaxis and eradication of coronavirus as claimed in claim 1, wherein the biochemical substance having a surface negative charge characteristic that is typically available to inactivate coronavirus is heparin sulfate or a sialic acid-type substance.

3. A novel method for the prophylaxis and eradication of coronavirus as claimed in claim 1 or 2, characterized in that the active substance is particulated and caused to act upon active inhalation by the use of aerosolized particles, and the substance or compound capable of inactivating coronavirus is caused to act upon active inhalation by the person or animal upon inhalation by nebulizing the particles with a solution thereof.

4. The novel method for the prevention and eradication of coronavirus according to claim 3, wherein the physical atomization of the substance or compound is achieved using an ultrasonic device; when the liquid is applied, a preset physical mode is adopted to realize the micronization of the liquid.

5. The method of claim 4, wherein the substances and compounds with potential surface negative charge characteristics are physically enhanced by a specific atomizer means, an electrostatic field applying means combined with a piezoelectric ultrasonic vibrator can generate ionized atomization function and make the substances or compounds with stronger surface negative charge.

6. The novel method for preventing and killing coronavirus according to claim 5, wherein said electrostatic field applying means is combined with a piezoelectric ultrasonic vibrator, wherein said medicinal liquid is atomized and negatively charged through a set of coaxial or non-coaxial parallel channels.

7. The novel method for preventing and killing coronavirus according to claim 2, wherein the negatively charged amino acids aspartic acid (Asp) and glutamic acid (Glu) are amino acids having an excess carboxyl group, which are dissociated from hydrogen protons in an alkaline aqueous solution to form negatively charged amino acid radical ions, and are capable of forming negatively charged atomized droplets during electrospray ionization or ultrasonic atomization.

8. The method of claim 2, wherein the defensin is a type of disulfide-rich cationic polypeptide which is itself an antibacterial peptide with direct bactericidal activity produced during the course of the biological evolution; can also be used as a substance for preventing virus invasion; the positive charge of the self-body blocks a region with strong negative charge, such as a strong negative charge structural domain of ACE2 protein, so that a competitive binding recognition site is formed with coronavirus, and the infection probability of the virus is further reduced.

9. The novel method for preventing and killing coronavirus according to claim 2, wherein some substances and compounds in the aqueous or alcoholic extract of glycyrrhiza acid, which is a traditional Chinese medicine, also have the effect of inactivating coronavirus by enhancing its surface negative charge characteristics.