CN114432280A - Application of Bronopol in preparation of anti-coronavirus infection medicine - Google Patents
Application of Bronopol in preparation of anti-coronavirus infection medicine Download PDFInfo
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- CN114432280A CN114432280A CN202011221941.XA CN202011221941A CN114432280A CN 114432280 A CN114432280 A CN 114432280A CN 202011221941 A CN202011221941 A CN 202011221941A CN 114432280 A CN114432280 A CN 114432280A
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- LVDKZNITIUWNER-UHFFFAOYSA-N Bronopol Chemical compound OCC(Br)(CO)[N+]([O-])=O LVDKZNITIUWNER-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229960003168 bronopol Drugs 0.000 title claims abstract description 28
- 239000003814 drug Substances 0.000 title claims abstract description 28
- 208000001528 Coronaviridae Infections Diseases 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims description 4
- 241000711573 Coronaviridae Species 0.000 claims abstract description 34
- 101800000504 3C-like protease Proteins 0.000 claims abstract description 26
- 101800001016 Picornain 3C-like protease Proteins 0.000 claims abstract description 21
- 101800000596 Probable picornain 3C-like protease Proteins 0.000 claims abstract description 21
- 230000005764 inhibitory process Effects 0.000 claims abstract description 8
- 239000003112 inhibitor Substances 0.000 claims description 21
- 229940079593 drug Drugs 0.000 claims description 12
- 241000315672 SARS coronavirus Species 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 241000127282 Middle East respiratory syndrome-related coronavirus Species 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- 241000711467 Human coronavirus 229E Species 0.000 claims description 4
- 241000482741 Human coronavirus NL63 Species 0.000 claims description 4
- 241001428935 Human coronavirus OC43 Species 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000000839 emulsion Substances 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 235000011054 acetic acid Nutrition 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- 235000011007 phosphoric acid Nutrition 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 241001678559 COVID-19 virus Species 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 17
- 102000004190 Enzymes Human genes 0.000 abstract description 7
- 108090000790 Enzymes Proteins 0.000 abstract description 7
- 229940125673 3C-like protease inhibitor Drugs 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 10
- 108091005804 Peptidases Proteins 0.000 description 9
- 239000004365 Protease Substances 0.000 description 9
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 9
- 108090000765 processed proteins & peptides Proteins 0.000 description 9
- 239000000243 solution Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 4
- 229910021538 borax Inorganic materials 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000004328 sodium tetraborate Substances 0.000 description 4
- 235000010339 sodium tetraborate Nutrition 0.000 description 4
- 230000005284 excitation Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 208000025370 Middle East respiratory syndrome Diseases 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 230000008014 freezing Effects 0.000 description 2
- 238000007710 freezing Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 101800000535 3C-like proteinase Proteins 0.000 description 1
- 101800002396 3C-like proteinase nsp5 Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000025721 COVID-19 Diseases 0.000 description 1
- 102000005927 Cysteine Proteases Human genes 0.000 description 1
- 108010005843 Cysteine Proteases Proteins 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000009525 Myocarditis Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 101800000508 Non-structural protein 5 Proteins 0.000 description 1
- 108010076039 Polyproteins Proteins 0.000 description 1
- 101710153041 Replicase polyprotein 1a Proteins 0.000 description 1
- 101710151619 Replicase polyprotein 1ab Proteins 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- -1 adsorption carrier Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
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- 241001493065 dsRNA viruses Species 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
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- 239000000945 filler Substances 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
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- 231100000053 low toxicity Toxicity 0.000 description 1
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- 230000029812 viral genome replication Effects 0.000 description 1
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/047—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates having two or more hydroxy groups, e.g. sorbitol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/26—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups and being further substituted by halogen atoms
Abstract
The invention discloses an application of Bronopol in preparing a medicine for resisting coronavirus infection and an application in preparing a coronavirus 3C-like protease 3Clpro inhibitor medicine, wherein Bronopol has a strong inhibition effect on the enzyme activity of a target 3C-like protease 3Clpro of coronavirus, and has the potential of developing into a medicine for treating and preventing coronavirus, particularly resisting new coronavirus.
Description
Technical Field
The invention relates to the technical field of medicinal chemistry, in particular to application of Bronopol in preparation of a coronavirus infection resisting medicine.
Background
Coronaviruses belong to the single positive strand RNA virus, and the family of coronaviruses mainly includes novel coronaviruses (SARS-CoV-2), SARS coronaviruses (SARS-CoV), middle east respiratory syndrome coronaviruses (MERS-CoV), HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU. Coronaviruses commonly cause respiratory and intestinal diseases, neurological symptoms, and myocarditis. In 2003, severe upper respiratory disease (SARS) outbreaks, infected with about 8000 people worldwide, with mortality rates as high as 10%. In 2014, Middle East Respiratory Syndrome (MERS) was outbreak in many countries around the world with mortality rates higher than SARS-CoV, reaching approximately 40%. By the end of 2019, a novel coronavirus (COVID-19) outbreak, and the novel strain (SARS-CoV-2) has lower fatality rate than SARS-CoV-1 in 2003 but has stronger infection capacity. To date, the number of infected people worldwide is nearly 1000 thousands, the death is nearly 100 thousands, and the epidemic situation continues to ferment. The infection of these diseases seriously affects the health of people and the development of economy. The repeated outbreaks of coronaviruses suggest that human beings are poorly informed about their research and the development of drugs for treating new coronaviruses is imminent.
3C-like protease (3CLpro) is a hydrolase expressed on the 5' end genome of coronavirus nsp5, and mainly functions to cleave at least 11 sites on polyproteins pp1a and pp1ab, which need to be processed into mature functional proteins after being hydrolyzed; the 3C-like protease (3CLpro) is a cysteine protease that recognizes sequences with Leu and Glin at positions P2 and P1, respectively. In addition, the substrate binding site of the 3C-like protease (3CLpro) is highly conserved and plays a key role in mediating virus replication and transcription, so the 3CL protease can be used as an ideal target point for designing and screening the anti-coronavirus infection medicines.
Bronopol, known as Bronopol in chinese, is an antibacterial agent with low toxicity (to mammals) and high activity (especially to gram-negative bacteria). After examining the relevant data, no report about Bronopol as a novel coronavirus 3CLpro inhibitor is found.
Disclosure of Invention
In order to solve the technical problems, the invention provides an application of Bronopol in preparing a medicine for resisting coronavirus infection, so as to achieve the aim of effectively inhibiting the activity of coronavirus 3C-like protease 3 Clpro.
In order to achieve the purpose, the technical scheme of the invention is as follows:
application of Bronopol in preparing anti-coronavirus infection medicines.
In the above scheme, the Bronopol has a structure represented by formula (I),
in the above scheme, the Bronopol includes optical isomers thereof, hydrates thereof, and pharmaceutically acceptable salts thereof with acids.
In the scheme, the number of crystal water of the hydrate is any real number from 1 to 16.
In the above scheme, the coronavirus is HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU, SARS-CoV, MERS-CoV, or novel coronavirus SARS-CoV-2.
In the scheme, the acid is one or more of hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid and malic acid.
Application of Bronopol in preparing coronavirus 3C-like protease 3Clpro inhibitor medicine.
An inhibitor drug of the coronavirus 3C-like protease 3Clpro, said inhibitor drug comprising Bronopol or a pharmaceutically acceptable salt thereof.
In the scheme, the medicine is an injection, a tablet, a pill, a capsule, a suspending agent or an emulsion.
In the scheme, the administration route of the medicine is oral administration, percutaneous, intravenous or intramuscular injection
Through the technical scheme, the application of Bronopol in preparing the anti-coronavirus infection medicine and the application in preparing the coronavirus 3C-like protease 3Clpro inhibitor medicine has strong inhibition effect on the enzyme activity of the target 3C-like protease 3Clpro of the coronavirus, and has the potential of developing into the medicine for treating and preventing the coronavirus, particularly the anti-new coronavirus.
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 embodiments or the prior art descriptions will be briefly described below.
FIG. 1 is a graph of the fluorescence intensity of the substrate peptide at different concentrations of the inhibitor Bronopol as a function of time under the metabolism of the 3C-like protease 3 Clpro;
FIG. 2 is a graph showing the inhibition curve of Bronopol inhibitor against 3Clpro, a novel coronavirus 3C-like protease.
Detailed Description
The technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings in the embodiments of the present invention.
The technology of the invention is based on the three-dimensional structure of the novel coronavirus 3CLpro to carry out drug design, and thousands of compounds including a natural product library, a clinical compound library and an antiviral drug library are theoretically screened to obtain the compound which can inhibit the novel coronavirus 3 CLpro. Then, the enzyme activity test was performed using a commercially available 3CLpro fluorescent probe construction method, and used for inhibitor screening.
Through drug screening according to the scheme, the invention discovers the inhibition effect of the compound Bronopol and the pharmaceutically acceptable salt thereof (formula I) on SARS-CoV-23 CL protease as follows:
the compounds of formula (I) may be combined with pharmaceutically acceptable adjuvants and used in the manufacture of medicaments for the treatment and prophylaxis of novel coronavirus infections. The adjuvant comprises diluent, excipient, filler, binder, wetting agent, disintegrating agent, absorption enhancer, surfactant, adsorption carrier, lubricant, and synergist. The medicine can be made into injection, tablet, pill, capsule, suspension or emulsion. The administration route can be oral, percutaneous, intravenous or intramuscular injection.
In carrying out the experiment, all the procedures and procedures, reaction conditions of the substrate, and the like are designed and carried out according to methods well known to those skilled in the art.
In the examples below, inhibitor molecules were used, available from mce (medchemexpress) or other common commercial sources.
SARS-Cov-23C-like protease used in the present invention was purchased from CrystalO Biopharma, and substrate Dabcyl-KTSAVLQ ↓.SGFRKM-E (Edans) -NH2Purchased from GL biochem and borate borax buffer from reilian organisms. SARS-Cov-23C-like protease (concentration 0.1mg/mL), substrate peptide Dabcyl-KTSAVLQ ↓ ] SGFRKM-E (Edans) -NH2 (concentration 0.1mM-5mM), borax borate buffer (pH ═ 5-8). The invention requires fluorescence detection with a fluorescence microplate reader.
Example 1
Fluorescence intensity of substrate peptide under 3C-like protease metabolism with time at different inhibitor concentrations
The specific implementation process comprises the following steps:
1) storing the SARS-Cov-23C-like protease and substrate peptide stock solution in a refrigerator at-80 ℃;
2) melting SARS-Cov-23C-like protease in a freezing plate (-4 to 4 ℃) at room temperature, diluting 1uL into 98uL borax borate buffer solution (PH 7.4), and adding into a detection plate;
3) adding 1uL of inhibitors (Bronopol, concentration of 0, 0.1mM, 0.2mM, 0.5mM, 1mM) with different concentrations into the solution obtained in the step (2);
4) adding 1uL of substrate peptide (0.5mM) with the same concentration into the solution obtained in the step (3), incubating at 37 ℃ by using a fluorescence microplate reader, monitoring 342nm excitation by using the fluorescence microplate reader, detecting the fluorescence emission value at 496nm while incubating, and taking one point every 1 minute;
5) the slow increase in fluorescence intensity of the substrate peptide in the presence of the inhibitor under the enzyme metabolism over time is shown in FIG. 1, and the results show that the increase in fluorescence produced by the enzyme catalysis of the substrate peptide can be inhibited by the inhibitor Bronopol, and that this inhibition phenomenon is concentration-dependent.
Example 2
Determination of the inhibitory Capacity of Compound Bronopol on SARS-Cov-23C-like protease
The specific implementation process is as follows:
1) storing the SARS-Cov-23C-like protease and substrate peptide stock solution in a refrigerator at-80 ℃;
2) melting SARS-Cov-23C-like protease in a freezing plate (-4 to 4 ℃) at room temperature, diluting 1uL into 98uL borax borate buffer solution (PH 7.4), and adding into a detection plate;
3) adding 1uL of inhibitors (Bronopol, concentration of 0, 0.1mM, 0.2mM, 0.5mM, 1mM) with different concentrations into the solution obtained in the step (2);
4) adding 1uL of substrate peptide (0.5mM) with the same concentration into the solution obtained in the step (3), incubating at 37 ℃ by using a fluorescence microplate reader, monitoring 342nm excitation by using the fluorescence microplate reader, detecting the fluorescence emission value at 496nm while incubating, and incubating for 1 h;
5) and counting the fluorescence emission value at 496nm after 342nm excitation before and after incubation of each group. The fluorescence change values before and after incubation of the control group (inhibitor concentration 0 group) were taken as 100, and the Residual Activity values (Residual Activity) were obtained by comparing the fluorescence change values before and after incubation of the different inhibition groups. The inhibition ability of the compound can be obtained by plotting the ratio of the concentration of the inhibitor to the Activity of the inhibited enzyme by using GraphPad Prism6 software and plotting the logarithm of the concentration of the inhibitor (logC (inhibitor)) as the abscissa and the corresponding Residual Activity (Residual Activity) as the ordinate, as shown in FIG. 2, and as shown in FIG. 2, the concentration of the inhibitor at which the Activity of the inhibited enzyme is half is used as the expression.
As can be seen, the compound has obvious inhibiting effect on the novel coronavirus 3C-like protease, and IC50The value was 0.4371. mu.M, indicating that Bronopol is effective in inhibiting the activity of the novel coronavirus 3C-like protease. Moreover, the coronavirus 3C-like protease is shown to have high similarity based on sequence analysis, so the compound can also effectively inhibit the activity of other coronavirus 3C-like proteases, especially SARS-CoV, MERS-CoV, HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU 1.
IC50The formula is calculated as Y ═ 100/(1+10^ ((X-LogIC50))), where Y represents the residual activity fraction, X represents the common logarithm of the concentration of inhibitor compound, and Λ refers to the power algorithm.
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
- Application of Bronopol in preparing anti-coronavirus infection medicines.
- 3. use according to claim 1, wherein the Bronopol comprises optical isomers thereof, hydrates thereof, and pharmaceutically acceptable salts with acids.
- 4. The use according to claim 3, wherein the hydrate has a water of crystallization number of any real number from 1 to 16.
- 5. The use of claim 1, wherein the coronavirus is HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU, SARS-CoV, MERS-CoV, or a novel coronavirus SARS-CoV-2.
- 6. The use according to claim 3, wherein the acid is one or more of hydrochloric acid, sulfuric acid, hydrobromic acid, phosphoric acid, acetic acid, citric acid, oxalic acid, tartaric acid, benzoic acid, malic acid.
- Use of Bronopol for the preparation of a medicament for the inhibition of coronavirus 3C-like protease 3 Clpro.
- 8. An inhibitor drug of the coronavirus 3C-like protease 3Clpro, wherein said inhibitor drug comprises Bronopol or a pharmaceutically acceptable salt thereof.
- 9. The inhibitor drug for coronavirus 3C-like protease 3Clpro according to claim 8, wherein the drug is an injection, a tablet, a pill, a capsule, a suspension or an emulsion.
- 10. The inhibitor drug for coronavirus 3C-like protease 3Clpro according to claim 8, wherein the drug is administered by oral, transdermal, intravenous or intramuscular injection.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101933521A (en) * | 2009-07-01 | 2011-01-05 | 李新建 | Preparation and application thereof of sterilization composition |
CN104208049A (en) * | 2013-05-29 | 2014-12-17 | 李志海 | Application of bronopol and analogue thereof in drug preparation |
WO2015162238A1 (en) * | 2014-04-24 | 2015-10-29 | Paul Boye Technologies | Mask having an outer surface made of nonwoven polypropylene impregnated with bronopol |
CN113289018A (en) * | 2020-02-21 | 2021-08-24 | 中国科学院上海药物研究所 | Application of old medicine such as auranofin and composition thereof in resisting single positive strand RNA virus |
-
2020
- 2020-11-05 CN CN202011221941.XA patent/CN114432280A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101933521A (en) * | 2009-07-01 | 2011-01-05 | 李新建 | Preparation and application thereof of sterilization composition |
CN104208049A (en) * | 2013-05-29 | 2014-12-17 | 李志海 | Application of bronopol and analogue thereof in drug preparation |
WO2015162238A1 (en) * | 2014-04-24 | 2015-10-29 | Paul Boye Technologies | Mask having an outer surface made of nonwoven polypropylene impregnated with bronopol |
CN113289018A (en) * | 2020-02-21 | 2021-08-24 | 中国科学院上海药物研究所 | Application of old medicine such as auranofin and composition thereof in resisting single positive strand RNA virus |
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