CN117357558A - Application of two-dimensional nanomaterial CIPS in inhibition of coronavirus variant strain - Google Patents
Application of two-dimensional nanomaterial CIPS in inhibition of coronavirus variant strain Download PDFInfo
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Abstract
The invention provides application of a two-dimensional nanomaterial CIPS in inhibiting coronavirus variant strains, and particularly discloses application of the two-dimensional nanomaterial CIPS in preparing a medicament for treating or preventing diseases caused by coronavirus SARS-CoV-2 variant strains or a material for adsorbing or inhibiting coronavirus SARS-CoV-2 variant strains, wherein the coronavirus SARS-CoV-2 variant strains are selected from variant strains delta, variant strains omicron, variant strains beta and variant strains alpha. The material disclosed by the invention is simple to prepare, high in biological safety and excellent in effect.
Description
Technical Field
The invention belongs to the technical field of antivirus, and particularly relates to application of a two-dimensional nanomaterial CIPS in inhibiting coronavirus variant strains.
Background
The pneumonia (COVID 19) caused by the novel coronavirus (SARS-CoV-2) not only threatens human health but also causes immeasurable loss to global economy, especially the strain continuously generates new mutation with the lapse of time, and the uncontrollability of epidemic situation is further increased
Currently, a new coronavaccine worldwide is a major means of preventing viral infection. However, mutations in variant delta (variants of concern, VOCs), variant omacron and variant deltaacron (supermixed strains of delta and omacron) potentiate the pathogenicity, transmissibility and infectivity of the virus. Although the variant deltaacron is currently less known, a large number of mutation sites have been found in the variant omacron, which are more infectious and can be rapidly propagated in a short time. Over time, the mutation sites of viruses may also be more and more numerous, which also aggravates another concern: the large number of mutations produced by viruses has reduced the effectiveness of current vaccines and antibodies. There are a great deal of research data showing that mutant strains such as mutant omicron can evade the neutralizing effect of antibodies. Therefore, there is an urgent need to develop novel safe and effective novel crown drugs having broad-spectrum antiviral effects (effective against mutant strains).
Disclosure of Invention
Aiming at the defects in the prior art, one aspect of the invention provides application of a two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano-sheet (CIPS) in preparing a medicament for treating or preventing diseases caused by coronavirus SARS-CoV-2 variant strain.
In the technical scheme of the invention, in the application, the medicine further comprises a pharmaceutically acceptable carrier or excipient.
In the above embodiments, the method further comprises administering a therapeutically effective amount of at least one additional therapeutic agent or combination thereof selected from the group consisting of corticosteroids, anti-inflammatory signal transduction modulators, β2-adrenoreceptor agonist bronchodilators, anticholinergic agents, mucolytic agents, hypertonic saline, and other agents for the treatment of coronaviridae virus infections; or mixtures thereof.
In a second aspect, the invention provides a pharmaceutical composition for treating or preventing diseases caused by coronavirus SARS-CoV-2 variant strain, wherein the pharmaceutical composition takes two-dimensional nanomaterial indium doped copper sulfide-phosphide nano-sheet (CIPS) as an active ingredient.
In the technical scheme of the invention, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.
In the technical scheme of the invention, the pharmaceutical composition further comprises a second active ingredient, wherein the second active ingredient is selected from corticosteroids, anti-inflammatory signal transduction modulators, beta 2-adrenoreceptor agonist bronchodilators, anticholinergic drugs, mucolytic agents, hypertonic saline and other drugs for treating coronaviridae virus infection; or mixtures thereof.
In the technical scheme of the invention, in the pharmaceutical composition, the preparation form of the pharmaceutical composition is selected from oral preparation, injection preparation, mucosa administration preparation, inhalant and external preparation.
In a third aspect, the invention provides a method of treating or preventing coronavirus SARS-CoV-2 variant infection comprising administering to a subject a therapeutically effective amount of two-dimensional nanomaterial indium-doped copper sulfide-nanosheets (CIPS).
In the technical scheme of the invention, in the method, the two-dimensional nanomaterial with the effective treatment amount is given in a preparation form, and the preparation also comprises a pharmaceutically acceptable carrier or excipient.
In embodiments of the present invention, the method further comprises the step of administering to the subject a therapeutically effective amount of a second active ingredient selected from the group consisting of corticosteroids, anti-inflammatory signal transduction modulators, β2-adrenoreceptor agonist bronchodilators, anticholinergic agents, mucolytic agents, hypertonic saline, and other agents for the treatment of coronaviridae virus infections; or mixtures thereof.
The fourth aspect of the invention provides the use of a two-dimensional nanomaterial indium doped copper sulfide phosphide nanosheet in the preparation of a formulation for inhibiting the binding of Spike protein of a coronavirus SARS-CoV-2 virus variant and the receptor ACE2 of a host cell thereof; preferably, the two-dimensional nanomaterial indium doped copper sulfide nanoplatelets inhibit its binding to the receptor ACE2 of its host cell by competing for binding to the RBD binding site of the Spike protein of coronavirus.
The invention also provides the application of the two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano sheet layer in preparation of a locus for competitive binding of RBD of Spike protein of coronavirus SARS-CoV-2 variant.
The fifth aspect of the invention provides the use of a two-dimensional nanomaterial indium doped copper sulfide and phosphide nanosheets in the preparation of a medicament for promoting the proteolytic degradation of a variant SARS-CoV-2 virus.
In the technical scheme of the invention, in the method, the two-dimensional nanomaterial is used for preparing a medicament for promoting coronavirus to decompose Spike protein in SARS-CoV-2 virus variant.
The sixth aspect of the invention provides the use of a two-dimensional nanomaterial indium doped copper sulfide and phosphide nanosheets in the preparation of a medicament for promoting the decomposition of RNA of a variant strain of SARS-CoV-2 virus.
The seventh aspect of the invention provides an application of a two-dimensional nanomaterial indium-doped copper sulfide and phosphorus nanosheet layer in preparing a material for inhibiting infection of coronavirus variants.
In an eighth aspect, the invention provides a material for inhibiting infection by a coronavirus variant, the material comprising two-dimensional nanomaterial indium-doped copper sulfide-phosphide nanoplatelets and a matrix.
In the technical scheme of the invention, in the materials, the materials are materials for preparing protective articles, and the protective articles are preferably masks, protective clothing, protective masks and protective caps.
In the technical scheme of the invention, in the material, the material is a coating.
In the technical scheme of the invention, in the material, the material is a disinfectant or personal care product.
In the technical scheme of the invention, in the material, the material is a packaging material.
In the technical scheme of the invention, in the material, the material is a filtering material.
In a ninth aspect, the present invention provides an article comprising two-dimensional nanomaterial indium doped copper phosphide nanoplatelets (CIPS);
the articles are selected from the group consisting of protective articles, coatings, disinfectants, personal care articles, packaging materials, or filtration devices;
preferably, the protective articles are masks, protective clothing, protective face masks and protective caps;
preferably, the coating is a suspension containing two-dimensional nano materials, and the coating can endow the surface to be attached with a coating layer containing two-dimensional nano materials;
preferably, the disinfectant is an environmental disinfectant, a no-wash hand sanitizer, a hand sanitizer and a detergent; more preferably, the disinfectant is used for surface disinfection of packaging materials, medical instruments, oral appliances, cosmetic appliances;
preferably, the packaging material is provided with a coating layer containing two-dimensional nano materials, or the packaging material is a composite material containing two-dimensional nano materials; more preferably, the packaging material is a packaging material for a pharmaceutical or food product, in particular for cold chain transport;
preferably, the filtering device is a device for air filtering, a device for water filtering and a device for mask filtering; more preferably, the filtering device is an air filtering net, and the surface of the air filtering net is provided with two-dimensional nano materials; more preferably, the filtering device is air filtering cotton, and the two-dimensional nanomaterial is attached to the air filtering cotton fiber.
In the above application, the variant strain of coronavirus SARS-CoV2 is selected from the group consisting of variant delta, variant omacron, variant beta and variant alpha.
In the technical scheme of the invention, the diseases caused by coronavirus SARS-CoV2 variant are diseases caused by coronavirus variant delta, variant omicron, variant beta, variant gamma and variant alpha infection.
In the technical scheme of the invention, the two-dimensional nanomaterial is a material with a length of one dimension in space being nano-sized; preferably, the material is 1-100nm long in one dimension in space, more preferably 1-10nm long in one dimension in space, 100-500nm long in other dimensions, or for example, 100nm, 200nm, 300nm, 400nm, 500nm long in other dimensions.
In conclusion, compared with the prior art, the invention has the following beneficial effects:
1. the two-dimensional nanomaterial CIPS nanosheet can inhibit cell infection of coronaviruses, can specifically adsorb and combine coronavirus infection targets, reduces infection efficiency of viruses, further reduces replication of the viruses in a host body, reduces the quantity of the coronaviruses, and can be used as a therapeutic drug for coronapatients.
The effect of CIPS in inhibiting SARS-CoV-2 virus infection is also applicable to various variant strains, which shows that CIPS has broad spectrum on inhibiting coronavirus.
The CIPS nano sheet can be specifically combined with coronavirus to inhibit infection of SARS-CoV-2 virus variant strain to host cell, so as to implement specific adsorption fixation of virus. Can be used for preparing medicines, can be applied to melt-blown cloth, cold storage coating and external packing coating or spray of a mask, can adsorb new coronaviruses and reduce the number of the infectious viruses, and plays a role in preventing the new coronaviruses.
4. The two-dimensional nanomaterial CIPS nanosheet has no influence on the survival rate of common cells, which indicates that the nanomaterial has high biological safety and low toxicity.
5. The two-dimensional nano material can be stored for a long time at room temperature to-20 ℃ and is convenient to store. The two-dimensional nano material has high stability, can be mixed with any auxiliary materials, can be compounded to prepare medicines and composite materials, and is not influenced by factors such as temperature, pH and the like.
6. The invention adopts inorganic nanometer materials, has no limitation on material sources, is suitable for large-scale mass production, and has low cost and small dosage.
7. The biofilm interference experiment of the invention is carried out in a solid and liquid environment, and proves that CIPS can be extremely strongly combined with RBD region of coronavirus S protein (see figure 3). It can be seen that the material of the present invention is capable of long-term binding to coronavirus variants, and is capable of acting as a material that adsorbs coronaviruses and prevents them from binding to host cells. Namely, the material can instantly realize the combination with coronavirus, and inhibit the combination of virus and host cell after combination.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows the measurement of cytotoxicity of CIPS by CCK-8. After incubation of different cells with different concentrations (0-160. Mu.g/mL) of CIPS for 24h, the measurement of cell activity by CCK-8.
FIG. 2 is a graph showing quantitative detection of infection efficiency of SARS-CoV-2 on Vero-E6 cells. SARS-CoV-2 and CIPS with different concentration (0-160 mug/mL) are infected into Vero-E6 cells for 2h, redundant viruses are washed off, and the amount of the viruses is quantitatively detected after 40 h. Statistical analysis using ANOVA,: p <0.05,: p <0.01,: p <0.001.
FIG. 3 shows the binding force of BLI to RBD of different mutants in CIPS.
FIG. 4 is a computer simulation of the detection of binding force of CIPS to RBDs of different mutants. Wherein a) the configuration and adsorption interface of the wild-type RBD and the RBD of the mutant strain. The spheres represent mutated amino acid residues in RBD; the bottom layer is the amino acid residues that interface with CIPS binding. b-c) interaction force (b) of RBD with CIPS contacts atomic number (c).
Fig. 5 is a computer simulation of detection of binding sites of CIPS occupied omicron RBD to ACE 2. Upper row: the binding of omicron RBD to ACE2 and its binding interface were simulated in silico, with boxes displaying amino acids interacting with the binding interface. The following rows: the binding of omicron RBD to CIPS was simulated in silico. The enlarged right panels show amino acid residues at the binding interface, indicating that the amino acid residues to which omicron RBD binds ACE2 overlap with the amino acid residues to which omicron RBD binds CIPS.
Detailed Description
The following detailed description of the present invention will be made in detail to make the above objects, features and advantages of the present invention more apparent, but should not be construed to limit the scope of the present invention.
Terminology
In the present invention, indium doped copper phosphide with copper indium phosphide, CIPS or CuInP 2 S 6 Has the same meaning.
In the present invention, the terms "nanoplatelets" and "two-dimensional nanomaterial" have similar meanings, and each refers to a material having one dimension in space that is nano-scale, such as a nanomaterial having a thickness dimension of 1-100 nm. In the present invention, the two-dimensional nanomaterial is indium doped copper sulfide phosphide nanoplatelets (CIPS). In a preferred embodiment, the dimensions of each two-dimensional nanomaterial are selected to be: the thickness (one dimension in space) is 1-10nm. The dimension of the nanoplatelets perpendicular to the thickness direction (other dimensions in space) is 100-300nm.
The "nanoplatelets" can be exfoliated by methods conventional in the art to obtain nanoplatelet materials, such as by mechanical milling (e.g., ball milling), ultrasound, and the like.
"pharmaceutically acceptable carrier or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye/colorant, taste enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonizing agent, solvent, or emulsifying agent that has been approved by the food and drug administration as acceptable for use in humans or livestock.
"pharmaceutical composition" refers to a formulation of a compound of the invention and a vehicle commonly accepted in the art for delivery of a biologically active compound to a mammal (e.g., a human). Such vehicles include all pharmaceutically acceptable excipients therefor.
An "effective amount" or "therapeutically effective amount" refers to an amount of a compound according to the present invention that, when administered to a patient in need thereof, is sufficient to effect treatment of a disease state, condition, or disorder that has utility for the two-dimensional nanomaterial. Such an amount will be sufficient to elicit the biological or medical response of the tissue system or patient sought by the researcher or clinician. The amount of a compound according to the invention that constitutes a therapeutically effective amount will vary depending on factors such as: the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of the treatment, the type of the disease state or condition being treated and its severity, the drug to be combined with or used in conjunction with the compound of the invention, and the age, weight, general health, sex, and diet of the patient. Such therapeutically effective amounts can be routinely determined by one of ordinary skill in the art based on their own knowledge, prior art, and the present disclosure.
The term "treating" as used herein, unless otherwise indicated, refers to reversing, alleviating, inhibiting the progression of, or preventing a disorder or condition to which such term applies, or one or more symptoms of such disorder or condition. The term "treatment" as used herein refers to the act of treatment, as "treatment" is as described immediately above. In some embodiments, the term "treating" is intended to mean administering a two-dimensional nanomaterial or composition thereof according to the present invention to reduce or eliminate symptoms of coronavirus infection and/or reduce viral load in a patient.
"prevention" (prevention or presntation) refers to any treatment of a disease or disorder that results in the clinical symptoms of the disease or disorder not developing. The term "preventing" also includes the administration of a therapeutically effective amount of a compound or composition according to the invention (e.g., pre-exposure prevention) prior to exposure of an individual to a virus to prevent symptoms of the disease from occurring and/or to prevent the virus from reaching a detectable level in the blood.
The term "subject" or "patient" refers to an animal, such as a mammal (including a human), that has been or is to be the subject of treatment, observation or experiment. The methods described herein may be used for human therapeutic and/or veterinary applications. In some embodiments, the subject is a mammal (or patient). In some embodiments, the subject (or patient) is a human, livestock (e.g., dogs and cats), farm animals (e.g., cows, horses, sheep, goats, and pigs), and/or laboratory animals (e.g., mice, rats, hamsters, guinea pigs, rabbits, cats, dogs, and monkeys). In some embodiments, the subject (or patient) is a human. A "person (or patient) in need thereof" refers to a person who may have or is suspected of having a disease or condition that would benefit from certain treatments; for example, treatment according to the present application with a two-dimensional nanomaterial disclosed herein or a composition thereof or a pharmaceutical composition comprising the above ingredients.
Pharmaceutical preparation
The two-dimensional nanomaterial of the present invention is formulated with conventional carriers and excipients, which will be selected according to conventional practice. The tablets will contain excipients, glidants, fillers, binders and the like. Aqueous formulations are prepared in sterile form and are intended to be generally isotonic by delivery other than oral administration.
Although the active ingredient two-dimensional nanomaterials can be administered alone, it may be preferable to present them as pharmaceutical formulations. The formulations of the invention for veterinary and human use comprise at least one active ingredient as defined above, said active ingredient being a two-dimensional nanomaterial: indium doped copper sulphur phosphide nanoplatelets (CIPS), together with one or more acceptable carriers and optionally other therapeutic ingredients, such as corticosteroids, anti-inflammatory signal transduction modulators, β2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline and other drugs for the treatment of coronaviridae virus infections; or mixtures thereof.
Formulations of the present invention suitable for oral administration may be presented as discrete units, such as capsules, cachets or tablets, each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or suspension in an aqueous or non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. Or prepared into oral administration preparations by other known techniques.
Tablets are prepared by compression or moulding, optionally with one or more accessory ingredients. Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules optionally mixed with a binder, lubricant, inert diluent, preservative, surfactant or dispersing agent. Molded tablets may be made by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent. The tablets may optionally be coated or scored and optionally formulated so as to provide slow or controlled release of the active ingredient therefrom.
The pharmaceutical composition of the present invention may be an external preparation such as an ointment for topical administration. For infections of the eye or other external tissues, such as the oral cavity and skin, the formulation is preferably as a topical ointment or cream containing the active ingredient. When formulated as ointments, the active ingredients may be used with paraffin or water-miscible ointment bases. Alternatively, the active ingredient may be formulated as a cream with an oil-in-water cream base. If desired, topical formulations may include compounds that enhance absorption or penetration of the active ingredient through the skin or other affected area. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogues. The oil phase of the emulsions of the present invention may be composed of known ingredients in known manner. The oil phase may comprise only emulsifiers, but it may also comprise a mixture of at least one emulsifier with a fat or oil or with both a fat and an oil. Preferably, a hydrophilic emulsifier is included together with a lipophilic emulsifier that acts as a stabilizer. Also preferably included are oils and fats.
The pharmaceutical compositions of the present invention may be in the form of sterile injectable preparations, for example, as aqueous or oleaginous suspensions for sterile injection.
The pharmaceutical compositions of the invention may be formulated for topical ocular administration and include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, in particular an aqueous solvent for the active ingredient.
The pharmaceutical compositions of the present invention may be in a formulation suitable for topical administration in the mouth including lozenges comprising the active ingredient in a flavoured base, typically sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerin or sucrose and acacia; and mouthwashes containing the active ingredient in a suitable liquid carrier.
The pharmaceutical compositions of the invention may be formulations for rectal administration which may be presented as suppositories with suitable matrices, e.g. containing cocoa butter or a salicylate.
The pharmaceutical compositions of the present invention may be formulations suitable for intrapulmonary or intranasal administration, such formulations typically having a particle size in the range of 0.1-500 microns, such as 0.5, 1, 30, 35 microns, etc., which are rapidly inhaled through the nasal passages or administered by oral inhalation to reach the alveoli. The active ingredients of the present invention have dimensions that can be used for intrapulmonary or intranasal administration, such as inhalants.
The pharmaceutical compositions of the present invention may be formulations suitable for parenteral administration including aqueous and nonaqueous sterile injection solutions which may contain antioxidants, buffers, bacteriostats and solutes which render the formulation isotonic with the blood of the intended recipient; and aqueous and non-aqueous sterile suspensions which may contain suspending agents and thickening agents.
Formulations of the pharmaceutical compositions of the present invention are presented in unit-dose or multi-dose containers, e.g., sealed ampules and vials, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of the sterile liquid carrier, e.g., water for injection, immediately prior to use. Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets of the kind previously described. Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose or suitable portion thereof of the active ingredient as described above.
The pharmaceutical composition of the invention may be a veterinary composition comprising at least one active ingredient as defined above and a veterinary carrier.
The compounds of the present invention are useful for providing controlled release pharmaceutical formulations containing as an active ingredient one or more of the active ingredients of the present invention, wherein the release of the active ingredient is controlled and regulated to allow less frequent administration or to improve the pharmacokinetic or toxicity profile of a given active ingredient.
Combination therapy
The medicaments, pharmaceutical compositions or active ingredients of the invention are also used in combination with other active ingredients. For the treatment of coronavirus infections, other active ingredients are active against coronavirus infections, in particular SARS or SARS-CoV-2 infections. Non-limiting examples of such other active therapeutic agents are corticosteroids, anti-inflammatory signal transduction modulators, β2-adrenoreceptor agonist bronchodilators, anticholinergic agents, mucolytic agents, hypertonic saline, and other drugs for the treatment of coronaviridae virus infections; or mixtures thereof.
The medicament, pharmaceutical composition or active ingredient of the invention may also be administered to a patient in unit dosage form in combination with one or more other active ingredients, either simultaneously or sequentially. The combination therapy may be administered as a simultaneous or sequential regimen. When administered sequentially, the combination may be administered in two or more administrations.
Co-administration of a drug, pharmaceutical composition or active ingredient of the invention with one or more other active ingredients generally refers to simultaneous or sequential administration of a compound of the invention and one or more other active therapeutic agents such that a therapeutically effective amount of the drug, pharmaceutical composition or active ingredient of the invention and one or more other active ingredients are present in the patient.
Combination therapy may provide "synergy" and "synergy", i.e., an effect that is greater than the sum of the effects produced by the compounds alone when used together. When the active ingredients are: (1) Co-formulated and when administered or delivered simultaneously in a combined formulation; (2) alternatively or in parallel delivery as separate formulations; or (3) through other schemes, a synergistic effect can be obtained.
An application scheme of the invention provides the application of the two-dimensional nanomaterial in preparing a material for inhibiting coronavirus infection; the two-dimensional nanomaterial is indium-doped copper sulfide and phosphide nano-sheet (CIPS).
An application scheme of the invention is to provide a material for inhibiting coronavirus infection, which comprises a two-dimensional nanomaterial and a matrix, wherein the two-dimensional nanomaterial is indium doped copper sulfide and phosphorus nano-sheet (CIPS).
In the above-mentioned scheme of coronavirus-inhibiting materials, the materials may further comprise matrixes, which can be changed according to the use, and since the two-dimensional nanomaterial of the present invention has high stability, it can be adapted to various matrixes, and materials of corresponding matrixes can be obtained according to the conventional methods in the art, including, but not limited to, compositing the two-dimensional nanomaterial with the matrixes by the following ways, and adsorbing the two-dimensional nanomaterial with the surface of the matrixes by adsorption; or blending the two-dimensional nanomaterial with a matrix, and then curing the matrix.
In the technical scheme of the invention, in the materials, the materials are materials for preparing protective articles, and the protective articles are preferably masks, protective clothing, protective masks and protective caps.
In the technical scheme of the invention, in the material, the material is a coating.
In the technical scheme of the invention, in the material, the material is a disinfectant.
In the technical scheme of the invention, in the material, the material is a packaging material.
In the technical scheme of the invention, in the material, the material is a filtering material.
In a particularly preferred embodiment, the material for inhibiting coronavirus infection is a material for preparing a mask, the material is a fabric, and the surface or the inside of the fabric contains the two-dimensional nanomaterial. In a variant of the preferred embodiment, the material for inhibiting coronavirus infection is a material for producing a mask, said material being a nonwoven, preferably a spunbond nonwoven or a meltblown nonwoven; the surface or the inside of the non-woven fabric contains the two-dimensional nano material. The preparation method of the material can adopt a method conventional in the field to compound the two-dimensional nano material with the matrix material. For example, the meltblown material may be combined with the two-dimensional nanomaterial before melt-blowing and spinning, and then melt-blown, or the obtained meltblown fabric may be combined with the two-dimensional nanomaterial.
In a particularly preferred embodiment, the coronavirus infection-inhibiting material is a coating that is a suspension comprising two-dimensional nanomaterial. Preferably, the paint further comprises at least one of a surfactant and a thickener. The coating is capable of imparting a two-dimensional nanomaterial to a surface of an object, such as a packaging surface, a medical device surface, a cosmetic device surface, or the like, such that it forms a coating comprising the two-dimensional nanomaterial on the surface of the object. In a specific embodiment, the coating imparts a coating of two-dimensional nanomaterial to the surface of the exterior or interior package of the food or pharmaceutical product, preferably where cold chain transport is desired.
In a particularly preferred embodiment, the coronavirus infection-inhibiting material is a disinfectant, which is a suspension comprising two-dimensional nanomaterial. In a particularly preferred embodiment, the disinfectant is an environmental disinfectant, a leave-on hand wash, a detergent. In a particularly preferred embodiment, the disinfectant is a surface disinfectant that can be used for packaging materials, medical devices (e.g., catheters, injection needles, surgical instruments, surgical masks, and other medical devices), oral devices (e.g., dentures, protective strips, padding, palate dilators), cosmetic devices (e.g., beauty instruments, orthopedic devices). In a particularly preferred embodiment, the concentration of the two-dimensional nanomaterial in the disinfectant is in the range of 1 μg/mL to 1000 μg/mL, preferably 2.5 to 160 μg/mL, more preferably 20 μg/mL to 160 μg/mL.
In a particularly preferred embodiment, the coronavirus infection-inhibiting material is a packaging material, and the packaging material is used for a drug or food for cold chain transport or storage. The surface of the packaging material is provided with a coating containing two-dimensional nano materials, or the packaging material is a composite material containing two-dimensional nano materials.
In a particularly preferred embodiment, the material for inhibiting coronavirus infection is a filter material, and the filter material is a material for air filtration, a material for water filtration, or a material for mask filtration. In a particularly preferred embodiment, the filter material is an airstrainer, and the surface of the airstrainer is provided with two-dimensional nanomaterial. In a particularly preferred embodiment, the filter material is air filter cotton, and the two-dimensional nanomaterial is attached to the air filter cotton fibers. For example, the filter material can be used for any device or equipment requiring air filtration, such as air conditioning filtration, air purifier filtration, fresh air system filtration, and the like. The use scenario is not limited to home, office, laboratory, factory, etc.
In the solution of the present invention, in the above-mentioned use, the material is a solid, liquid or semi-solid material.
In the present invention, in the above-described applications, the liquid material is a paint containing a two-dimensional nanomaterial, a disinfectant containing a two-dimensional nanomaterial, or a personal care product containing a two-dimensional nanomaterial.
In the present invention, in the above-mentioned application, the solid material is a device or a packaging material having a surface containing two-dimensional nanomaterial.
In the present invention, in the above-mentioned use, the semisolid material is a gel containing two-dimensional nanomaterial.
The present invention is described below by way of specific examples to demonstrate the nanomaterial indium doped copper sulfide phospho nanoplatelets (CIPS or CuInP 2 S 6 ) Influence on cell viability, inhibition of SARS-CoV-2 virus mutant by CIPS nanosheets on cell invasion, and binding of CIPS to novel coronavirus RBD protein.
The experimental materials used in the following examples include HBE cells, A549 cells, pHEK-Ad cells, vero-E6 cells. Materials, reagents, vectors, strains, etc. used in the examples described below are commercially available unless otherwise specified.
ACE2 is also known as ACEH and is known as angiotensin converting enzyme 2. The protein coded by the gene belongs to the family of angiotensin converting enzymes of dipeptidyl carboxyl dipeptidase and has quite large homology with human angiotensin converting enzyme 1. The gene encoding protein is the functional receptor of SARS and SARS-CoV-2, HCoV-NL63 human coronavirus Spike glycoprotein.
Vero-E6 cells are an African green monkey kidney cell line, are one of the cells that have been validated as being infected by a novel coronavirus, and can be used as a cell host for the culture of the novel coronavirus. Such as: the effect of a drug on the replication rate of the new coronavirus is determined, and the presence of the new coronavirus is examined or the new coronavirus is cultured for research purposes.
Example 1 Synthesis method of indium-doped copper sulfide-phosphide nanosheets (CIPS)
CIPS single crystals are obtained through a purchase or known method, and CIPS nano-sheets are obtained through mechanical grinding and other mechanical stripping experiments, wherein the thickness of the indium-doped copper sulfide nano-sheets is about 1-10nm. The thickness of the nano-sheet layer is 100-300nm in the vertical direction. Known methods are as follows:
1) Adding P, S, in, cu and other compounds into a vacuum quartz tube according to a chemical dosage ratio, and reacting for 2 weeks at 600 ℃ by a chemical migration method;
2) Obtaining a yellow and uniform block single crystal sample in which air can exist stably;
3) Peeling the single crystal by mechanical grinding and other mechanical methods to obtain a slice;
4) The ultrasonic probe ultrasonically processes the sheet to obtain nano-sheets of several hundred nanometers in thickness.
Example 2 detection of toxicity to cells
The cytotoxicity of CIPS on HBE cells, A549 cells and pHEK-Ad cells was examined using CCK-8 as follows:
HBE cells, A549 cells and pHEK-Ad cells were seeded into 96-well plates at a density of 1X 10 4 cell/wall，37℃，5％CO 2 The culture was carried out overnight,
the medium was changed to medium containing different concentrations of CIPS (0, 1.25, 2.5, 5, 10, 20, 40, 80 and 160. Mu.g/mL) and incubated at 37℃for 24h.
mu.L of CCK-8 solution was added to each well at a ratio of 1:10, incubated for 30-60min, and absorbance at 450nm was measured.
Cell activity was calculated according to the following formula: cell activity= (a 450 Treatment group-A 450 Blank group)/(A 450 Control group-A 450 Blank) x 100%.
Different concentrations of CIPS nanomaterial are respectively incubated with different cells, and the cytotoxicity of the CIPS nanomaterial is detected by CCK-8. The results are shown in fig. 1, and the experimental results show that the survival rate of 0-160 mug/mL CIPS on HBE cells, A549 cells and pHEK-Ad cells is not significantly different from that of the CIPS at 0, which indicates that the CIPS has no cytotoxicity, in other words, the biocompatibility of the CIPS nano material is good, and the safety is high.
EXAMPLE 3 quantitative PCR of fluorescein to detect the Effect of CIPS on SARS-CoV-2 mutant infection with Vero-E6
vero-E6 cells were cultured as monolayer cells (2X 10) in 96-well plates 4 /hole).
The test drug CIPS was diluted to 2.5. Mu.g/mL, 5. Mu.g/mL, 10. Mu.g/mL, 20. Mu.g/mL, 40. Mu.g/mL, 80. Mu.g/mL, 160. Mu.g/mL with the cell maintenance solution in a double dilution method. The virus infection titer was 100TCID50; 5 wells were set for each drug concentration.
After the medicine is evenly mixed for 2min by shaking, the medicine and the virus are immediately added into cells after being evenly mixed, and the virus is adsorbed for 2h.
After that, discardAfter washing once with PBS, each well was supplemented with 0.2mL of a maintenance solution containing the drug. Cell control (maintenance solution only), drug control (no virus) and virus control (no drug solution) were simultaneously set. Placing at 37deg.C, 5% CO 2 Culturing in incubator.
Cell culture supernatants were harvested 48 hours later for viral nucleic acid extraction. The relative quantification of the virus was performed using a covd-19 fluorescent quantitative PCR kit (registered with clinical medical devices).
The viruses are true virus VOC alpha virus strain, VOC delta virus strain, VOC beta virus strain and VOC omicron virus strain. The experimental results of infection detection using the mutant strain of the real virus SARS-CoV-2 are shown in FIG. 2, and the experimental results show that the infection efficiency of the mutant strain of SARS-CoV-2 gradually decreases with increasing CIPS concentration (FIG. 2). Experimental results show that CIPS can inhibit infection of mutant strain of SARS-CoV-2.
Example 4 affinity and interaction of CIPS with RBD proteins of mutant Virus
The affinity and interaction of CIPS material with mutant RBD proteins of different SARS-CoV-2 was quantitatively determined using biological membrane interference (BLI). KD values were calculated for the different systems, all <0.001nM. The experimental results are shown in fig. 3, and the results show that CIPS can be combined with RBD of virus effectively, so that infection of virus is inhibited.
Example 5 in silico means to detect affinity and interaction of CIPS with RBD protein of mutant Virus
The interaction force and the number of bound atoms between CIPS material and mutant RBD proteins of different SARS-CoV-2 were determined by computer simulation. The experimental results are shown in fig. 4, and the results show that CIPS can be combined with RBD of virus in a strong way, so that infection of virus is inhibited, and the combination of CIPS and non-mutated RBD is not significantly different from the combination of mutated RBD, namely, the mutation of amino acid site of RBD does not affect the combination of CIPS and the same.
Example 6 in silico simulation means to detect amino acid sites of CIPS binding to omicron RBD
The amino acid positions at which CIPS material binds to the RBD protein of the SARS-CoV-2omicron mutant strain were determined by computer simulation. The experimental results are shown in fig. 5, and the results show that CIPS can occupy the amino acid site of the omicron mutant RBD protein combined with ACE2, so that the binding of viruses to the receptor ACE2 is inhibited. This suggests that CIPS is able to inhibit infection of host cells by viruses by inhibiting their RBD binding to ACE 2.
Claims (11)
1. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano sheet in preparing medicament for treating or preventing diseases caused by coronavirus SARS-CoV-2 variant strain;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha; the disease caused by coronavirus SARS-CoV2 variant is a disease caused by infection of any one or at least two of coronavirus variant delta, variant omicron, variant beta, variant gamma and variant alpha.
2. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano-sheet in preparation of preparation for inhibiting binding of Spike protein of coronavirus SARS-CoV-2 variant strain and receptor ACE2 of host cell;
preferably, the two-dimensional nanomaterial indium-doped copper sulfide-phosphide nanoplatelets inhibit their binding to the receptor ACE2 of their host cells by competing for binding to sites of RBD binding of coronavirus variant Spike protein;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one of variant delta, variant omicron, variant beta, variant gamma and variant alpha or a combination of at least two of the variant delta, variant omicron, variant beta, variant gamma and variant alpha.
3. Use of two-dimensional nanomaterial indium doped copper sulfide phosphide nanosheet in preparation of medicine for promoting decomposition of coronavirus SARS-CoV-2 variant protein;
preferably, the protein at least comprises a Spike protein;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
4. Use of two-dimensional nanomaterial indium doped copper sulfide phosphide nanosheet in preparation of medicine for promoting decomposition of RNA of coronavirus SARS-CoV-2 variant strain;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
5. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano sheet in preparing medicine for inhibiting coronavirus SARS-CoV-2 variant strain from infecting host cell;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
6. A pharmaceutical composition for treating or preventing diseases caused by coronavirus SARS-CoV-2 variant strain, wherein the pharmaceutical composition takes two-dimensional nanomaterial indium doped copper sulfide-phosphide nano-sheet as active ingredient;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
7. The pharmaceutical composition of claim 6, further comprising administering a therapeutically effective amount of at least one additional therapeutic agent or combination thereof selected from the group consisting of corticosteroids, anti-inflammatory signal transduction modulators, β2-adrenoreceptor agonist bronchodilators, anticholinergic agents, mucolytic agents, hypertonic saline, and other agents for the treatment of coronaviridae virus infections; or mixtures thereof;
preferably, the pharmaceutical composition is in a form selected from the group consisting of oral preparations, injectable preparations, mucosal preparations, inhalants, and external preparations;
preferably, the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.
8. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano-sheet in preparation of preparation or material for inhibiting binding of Spike protein of coronavirus SARS-CoV-2 variant strain and receptor ACE2 of host cell;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
9. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano sheet in preparing material for inhibiting infection of coronavirus SARS-CoV-2 variant or reducing and killing coronavirus SARS-CoV-2 variant;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha.
10. Application of two-dimensional nanomaterial indium doped copper sulfide and phosphorus nano-sheet in preparing and adsorbing coronavirus SARS-CoV-2 variant, or in preparing and decomposing coronavirus SARS-CoV-2 variant protein, or in preparing and decomposing coronavirus SARS-CoV-2 variant RNA material;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one or a combination of at least two of variant delta, variant omicron, variant beta, variant gamma and variant alpha;
preferably, the coronavirus SARS-CoV-2 variant protein comprises at least Spike protein.
11. A material for adsorbing or inhibiting coronavirus SARS-CoV-2 variants, the material comprising two-dimensional nanomaterial indium-doped copper sulfide-phosphide nanoplatelets and a matrix;
preferably, the coronavirus SARS-CoV-2 variant strain is selected from any one of variant delta, variant omicron, variant beta, variant gamma and variant alpha or a combination of at least two of the variant delta, variant omicron, variant beta, variant gamma and variant alpha.
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