CN113041249A - Application of caffeine in preparing medicine for inhibiting SARS-CoV-2 virus susceptibility - Google Patents

Abstract

The invention discloses medical application of caffeine. The use is (a) and/or (b) and/or (c) and/or (d) and/or (e) below: (a) use of caffeine in the manufacture of a product for the treatment of a disease caused by a coronavirus or a coronavirus infection; (b) use of caffeine in the preparation of a product for the prevention of a disease caused by a coronavirus or a coronavirus infection; (c) the application of caffeine in preparing products for inhibiting susceptibility of coronavirus; (d) use of caffeine in the manufacture of a product for reducing the risk of coronavirus infection; (e) use of caffeine in the preparation of a coronavirus inhibitor. According to the invention, the research shows that the caffeine can reduce the infection risk of SARS-CoV-2 virus.

Description

Application of caffeine in preparing medicine for inhibiting SARS-CoV-2 virus susceptibility

Technical Field

The invention belongs to the technical field of biological medicine, and particularly relates to application of caffeine in preparation of a medicine for inhibiting SARS-CoV-2 virus susceptibility.

Background

Coronaviruses (CoV) are widely present in nature and are RNA viruses with envelope, linear single-strand positive strand genome, which only infect vertebrates, are associated with a variety of diseases in humans and animals and can cause diseases in the respiratory, digestive and nervous systems of humans and animals. Viral pneumonia (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has become an emergent public health event of international concern.

Caffeine (Caffeine), also known as 1,3, 7-trimethylxanthine, is a plant alkaloid that is found in many plants. It inhibits the DNA repair ability of cells by inhibiting the kinase activity of ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related kinase). At present, the report of the caffeine as a medicine for preparing anti-coronavirus is not available.

Disclosure of Invention

The invention aims to provide medical application of caffeine.

The medical application of the caffeine provided by the invention is (a) and/or (b) and/or (c) and/or (d) and/or (e) as follows:

(a) use of caffeine in the manufacture of a product for the treatment of a disease caused by a coronavirus or a coronavirus infection;

(b) use of caffeine in the preparation of a product for the prevention of a disease caused by a coronavirus or a coronavirus infection;

(c) the application of caffeine in preparing products for inhibiting susceptibility of coronavirus;

(d) use of caffeine in the manufacture of a product for reducing the risk of coronavirus infection;

(e) use of caffeine in the preparation of a coronavirus inhibitor.

The product may be a medicament or a pharmaceutical formulation.

The coronavirus inhibitor can inhibit replication of coronavirus.

In the above applications, caffeine may be one of the active ingredients or the only active ingredient when preparing a medicament or pharmaceutical preparation.

In the above applications, caffeine may be used as one of the active ingredients or as the only active ingredient in the preparation of a medicament or pharmaceutical preparation.

In the above application, carrier material can also be added during preparation of the medicine.

Carrier materials include, but are not limited to, water-soluble carrier materials (e.g., polyethylene glycol, polyvinylpyrrolidone, organic acids, etc.), sparingly soluble carrier materials (e.g., ethyl cellulose, cholesterol stearate, etc.), enteric carrier materials (e.g., cellulose acetate phthalate, and carboxymethylcellulose, etc.). The materials can be prepared into various dosage forms, including but not limited to tablets, capsules, dripping pills, aerosols, pills, powders, solutions, suspensions, emulsions, granules, liposomes, transdermal agents, buccal tablets, suppositories, freeze-dried powder injections and the like. Can be common preparation, sustained release preparation, controlled release preparation and various microparticle drug delivery systems. In order to prepare the unit dosage form into tablets, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as starch, dextrin, calcium sulfate, lactose, mannitol, sucrose, sodium chloride, glucose, urea, calcium carbonate, kaolin, microcrystalline cellulose, aluminum silicate and the like; wetting agents and binders such as water, glycerin, polyethylene glycol, ethanol, propanol, starch slurry, dextrin, syrup, honey, glucose solution, acacia slurry, gelatin slurry, sodium carboxymethylcellulose, shellac, methyl cellulose, potassium phosphate, polyvinylpyrrolidone and the like; disintegrating agents such as dried starch, alginate, agar powder, brown algae starch, sodium bicarbonate and citric acid, calcium carbonate, polyoxyethylene, sorbitol fatty acid ester, sodium dodecylsulfate, methyl cellulose, ethyl cellulose, etc.; disintegration inhibitors such as sucrose, glyceryl tristearate, cacao butter, hydrogenated oil and the like; absorption accelerators such as quaternary ammonium salts, sodium lauryl sulfate and the like; lubricants, for example, talc, silica, corn starch, stearate, boric acid, liquid paraffin, polyethylene glycol, and the like. The tablets may be further formulated into coated tablets, such as sugar-coated tablets, film-coated tablets, enteric-coated tablets, or double-layer and multi-layer tablets. In order to prepare the dosage form for unit administration into a pill, various carriers well known in the art can be widely used. Examples of the carrier are, for example, diluents and absorbents such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, polyvinylpyrrolidone, kaolin, talc and the like; binders such as acacia, tragacanth, gelatin, ethanol, honey, liquid sugar, rice paste or batter, etc.; disintegrating agents, such as agar powder, dried starch, alginate, sodium dodecylsulfate, methylcellulose, ethylcellulose, etc. In order to prepare the unit dosage form into suppositories, various carriers known in the art can be widely used. As examples of the carrier, there may be mentioned, for example, polyethylene glycol, lecithin, cacao butter, higher alcohols, esters of higher alcohols, gelatin, semisynthetic glycerides and the like. In order to prepare the unit dosage form into preparations for injection, such as solutions, emulsions, lyophilized powders and suspensions, all diluents commonly used in the art, for example, water, ethanol, polyethylene glycol, 1, 3-propanediol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene sorbitol fatty acid esters, etc., can be used. In addition, for the preparation of isotonic injection, sodium chloride, glucose or glycerol may be added in an appropriate amount to the preparation for injection, and conventional cosolvents, buffers, pH adjusters and the like may also be added. In addition, colorants, preservatives, flavors, flavorings, sweeteners or other materials may also be added to the pharmaceutical preparation, if desired. The preparation can be used for injection administration, including subcutaneous injection, intravenous injection, intramuscular injection, intracavity injection and the like; for luminal administration, such as rectally and vaginally; administration to the respiratory tract, e.g., nasally; administration to the mucosa.

The invention also provides a medicament or pharmaceutical composition, the active ingredient of which comprises caffeine.

The medicament or the medicament composition has at least one of the following effects:

1) treating a disease caused by a coronavirus or a coronavirus infection;

2) preventing disease caused by coronavirus or coronavirus infection;

3) inhibiting susceptibility to coronavirus;

4) reducing the risk of coronavirus infection;

5) a coronavirus inhibitor.

The above-mentioned drugs or pharmaceutical compositions can be prepared into dosage forms such as solutions, tablets, capsules or injections according to conventional methods known to those skilled in the art.

The subject is administered an effective amount of caffeine when the caffeine is used to prevent and/or treat an infection caused by a coronavirus.

The invention also provides a method for inhibiting coronavirus infection of an animal, which comprises the following steps: caffeine is administered to the recipient animal to inhibit infection of the animal by the coronavirus.

The invention also provides a method for preventing diseases caused by coronavirus, which comprises the following steps: the administration of caffeine to a recipient animal is useful for preventing a disease caused by coronavirus.

The invention also provides a method for treating diseases caused by coronavirus, which comprises the following steps: the subject animals are administered caffeine to treat a disease caused by coronavirus.

In the present invention, the coronavirus may be a beta genus coronavirus, and specifically SARS-CoV-2.

In the present invention, the disease caused by coronavirus may be respiratory infection and/or digestive infection.

The respiratory system infection is respiratory tract infection and/or lung infection; the respiratory tract infection can be nasopharyngitis, rhinitis, pharyngolaryngitis, tracheitis and/or bronchitis; the pulmonary infection may be pneumonia; the digestive system infection may be diarrhea.

In the present invention, the diseases caused by coronavirus generally include viral pneumonia, severe acute respiratory syndrome, and the like.

In the present invention, the coronavirus infection usually causes viral pneumonia, severe acute respiratory syndrome and the like.

According to the invention, the research discovers that the caffeine can reduce the infection risk of SARS-CoV-2 virus, and has the potential for preparing anti-coronavirus medicines.

Drawings

FIG. 1 shows that the Caco-2 cells stably expressing Rluc and the Calu-3 cells 2 x 10 stably expressing Rluc⁴Inoculating 24-well plate, adding Caffein with final concentration of 1mM after cell adherencee, treating for 24 hours, then adding SARS-CoV-2-S pseudovirus MOI ═ 1 infected cells, collecting cells after 72 hours and detecting luciferase activity; panel A is Caco2 cell, and panel B is Calu3 cell.

Detailed Description

The present invention is described in further detail below with reference to specific embodiments, which are given for the purpose of illustration only and are not intended to limit the scope of the invention. The examples provided below serve as a guide for further modifications by a person skilled in the art and do not constitute a limitation of the invention in any way.

The experimental procedures in the following examples, unless otherwise indicated, are conventional and are carried out according to the techniques or conditions described in the literature in the field or according to the instructions of the products. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

Unless otherwise stated, the quantitative tests in the following examples were performed in triplicate, and the results were averaged.

Three packaging plasmids used in the following examples: PLP1, PLP2, VSV-G were purchased from Addgene.

Caco-2 (colorectal adenocarcinoma cells), Calu-3 cells (human lung adenocarcinoma cells) used in the examples described below were purchased from the cell center of the institute of basic medicine, university of Council, China.

Caffeine used in the following examples was purchased from Sigma.

Example 1 inhibition of SARS-CoV-2 susceptibility to cells by Caffeine

(I) constructing Caco-2 and Calu-3 cell lines stably expressing luciferase Rluc

To construct Caco-2 and Calu-3 cell lines stably expressing Renilla-luciferase (RLuc), we first packaged Rhuc-lentivirus particles (RLuc lentivirus expression vector pHHLVX-EF1 α -Rhuc-puro from Hedgehog Bio Science and Technology Ltd).

Firstly, HEK293T cells are cultured in a T-75 cell culture bottle by using 15ml of DMEM medium containing 10% fetal bovine serum until the density reaches 70%; then plasmid transfection was performed: a total of 20. mu.g of PLP1 (5.88. mu.g), PLP2 (2.8. mu.g), VSV-G (3.92. mu.g) and pHHLVX-EF 1. alpha. -Rluc-puro (7. mu.g), and 58.8. mu.l PEI (1mg/ml) were mixed in 1.5ml serum-free DMEM, reacted at room temperature for 15 minutes and added to HEK293T cells. Changing the liquid after 6 hours of transfection; after 48 hours of transfection, cell debris was removed by centrifugation at 1000g for 10 minutes, the supernatant was collected, then filtered through a 0.45 μ M filter, the filtrate was left at 4 ℃, 15ml of fresh DMEM medium was added to a T-75 cell culture flask, after 24 hours, the supernatant was collected and the filtrate was obtained as described above, the two filtrates were combined and 5 Xvirus concentrate (50% PEG-8000,1.5M NaCl) was added thereto, overnight at 4 ℃, then centrifuged at 2000x g 4 ℃ for 30 minutes, after carefully discarding the supernatant, the precipitate was resuspended in 500 μ l PBS. In order to further remove protein components in the serum, the precipitate is resuspended by PBS and then centrifuged at 12000g and 4 ℃ for 5 minutes to take the supernatant, and the obtained supernatant is the concentrated slow virus solution and is preserved at-80 ℃. The titer of the concentrated lentivirus was determined using the Lenti-pac HIV qRT-PCR Titration kit (GeneCopoeia) kit.

Adding the concentrated lentivirus solution into Caco2 cells and Calu3 cells respectively according to the MOI (molar equivalent of 1), changing the solution after infecting for 6 hours, adding puromycin with the final concentration of 2 mu g/ml after 48 hours for screening, wherein the surviving cells after 5 days are Caco-2 cells for stably expressing Rluc and Calu-3 cells for stably expressing Rluc.

(II) construction of pseudovirus comprising SARS-CoV-2S protein

1. Construction of SARS-CoV-2S protein expression plasmid

Inserting the double-stranded DNA molecule shown in the sequence 1 of the sequence table between KpnI and EcoRI enzyme cutting sites of the pcDNA3.0 vector to obtain the recombinant plasmid SARS-CoV-2-S. In sequence 1 of the sequence table, the 4 th to 3765 th nucleotides encode SARS-CoV-2S protein without C end 19 amino acid residues. The SARS-CoV-2S protein consists of 1273 amino acid residues. Deletion of the C-terminal 19 amino acid residues helps to enhance the ability of the protein to integrate into pseudovirions.

2. Construction of Luciferase expression plasmid

The double-stranded DNA molecule shown in sequence 2 of the sequence table was inserted between the NheI and BamHI cleavage sites of a pCDH-CMV-MCS-EF1-puro vector (purchased from SBI Co., Ltd.) to obtain a recombinant plasmid Luciferase (also referred to as recombinant plasmid pCDH-Luc). The 7 th-1659 th nucleotide of the recombinant plasmid Luciferase encodes Luciferase (Firefly Luciferase). Luciferase consists of 550 amino acid residues.

3. The packaging mode of the SARS-CoV-2-S pseudovirus packaging pseudovirus is basically the same as that of the Rluc lentivirus packaging, and the difference is only that: VSV-G was exchanged for SARS-CoV-2-S, and pHHLVX-EF1 α -Rluc-puro (7 μ G) was exchanged for pCDH-Luc (7 μ G).

The method comprises the following specific steps: firstly, HEK293T cells are cultured in a T-75 cell culture bottle by using 15ml of DMEM medium containing 10% fetal bovine serum until the density reaches 70%; then plasmid transfection was performed: a total of 20. mu.g of PLP1 (5.88. mu.g), PLP2 (2.8. mu.g), SARS-CoV-2-S (3.92. mu.g) and pCDH-Luc (7. mu.g), and 58.8. mu.l PEI (1mg/ml) were mixed in 1.5ml of serum-free DMEM, reacted at room temperature for 15 minutes and added to HEK293T cells. Changing the liquid after 6 hours of transfection; after 48 hours of transfection, cell debris was removed by centrifugation at 1000g for 10 minutes, the supernatant was collected, then filtered through a 0.45 μ M filter, the filtrate was left at 4 ℃, 15ml of fresh DMEM medium was added to a T-75 cell culture flask, after 24 hours, the supernatant was collected and the filtrate was obtained as described above, the two filtrates were combined and 5 Xvirus concentrate (50% PEG-8000,1.5M NaCl) was added thereto, overnight at 4 ℃, then centrifuged at 2000x g 4 ℃ for 30 minutes, after carefully discarding the supernatant, the precipitate was resuspended in 500 μ l PBS. In order to further remove protein components in the serum, the precipitate is resuspended by PBS and then centrifuged at 12000g and 4 ℃ for 5 minutes to take the supernatant, and the obtained supernatant is the concentrated SARS-CoV-2-S pseudovirus solution and is preserved at the temperature of 80 ℃.

(III) inhibition of pseudoviral infection by caffeine-treated cells

Caco-2 cells stably expressing Rluc and Calu-3 cells stably expressing Rluc were separately cultured at 2X 10 per well⁴After the cells are attached to the wall, caffeine with the final concentration of 1mM is added for 24 hours, then SARS-CoV-2-S pseudovirus MOI ═ 1 infected cells are added, and the cells are collected after 72 hours to detect luciferase activity. The results are shown in FIG. 1. As can be seen from FIG. 1, luciferase activity was significantly down-regulated after Caffeine treatment, which indicates that the amount of infected pseudovirus in Caffeine-treated cells was significantly reduced compared to that before treatment, and the result shows that Caffeine can reduce SARisk of infection by RS-CoV-2 virus.

SEQUENCE LISTING

<110> military medical research institute of military science institute of people's liberation force of China

Application of caffeine in preparation of medicine for inhibiting SARS-CoV-2 virus susceptibility

<160> 2

<170> PatentIn version 3.5

<210> 1

<211> 3768

<212> DNA

<213> Artificial sequence

<400> 1

accatgtttg tgttcctggt gctgctgcca ctggtgtcca gccagtgtgt gaacctgacc 60

accaggaccc aacttcctcc tgcctacacc aactccttca ccaggggagt ctactaccct 120

gacaaggtgt tcaggtcctc tgtgctgcac agcacccagg acctgttcct gccattcttc 180

agcaatgtga cctggttcca tgccatccat gtgtctggca ccaatggcac caagaggttt 240

gacaaccctg tgctgccatt caatgatgga gtctactttg ccagcacaga gaagagcaac 300

atcatcaggg gctggatttt tggcaccacc ctggacagca agacccagtc cctgctgatt 360

gtgaacaatg ccaccaatgt ggtgattaag gtgtgtgagt tccagttctg taatgaccca 420

ttcctgggag tctactacca caagaacaac aagtcctgga tggagtctga gttcagggtc 480

tactcctctg ccaacaactg tacctttgaa tatgtgagcc aaccattcct gatggacttg 540

gagggcaagc agggcaactt caagaacctg agggagtttg tgttcaagaa cattgatggc 600

tacttcaaga tttacagcaa acacacacca atcaacctgg tgagggacct gccacagggc 660

ttctctgcct tggaaccact ggtggacctg ccaattggca tcaacatcac caggttccag 720

accctgctgg ctctgcacag gtcctacctg acacctggag actcctcctc tggctggaca 780

gcaggagcag cagcctacta tgtgggctac ctccaaccaa ggaccttcct gctgaaatac 840

aatgagaatg gcaccatcac agatgctgtg gactgtgccc tggacccact gtctgagacc 900

aagtgtaccc tgaaatcctt cacagtggag aagggcatct accagaccag caacttcagg 960

gtccaaccaa cagagagcat tgtgaggttt ccaaacatca ccaacctgtg tccatttgga 1020

gaggtgttca atgccaccag gtttgcctct gtctatgcct ggaacaggaa gaggattagc 1080

aactgtgtgg ctgactactc tgtgctctac aactctgcct ccttcagcac cttcaagtgt 1140

tatggagtga gcccaaccaa actgaatgac ctgtgtttca ccaatgtcta tgctgactcc 1200

tttgtgatta ggggagatga ggtgagacag attgcccctg gacaaacagg caagattgct 1260

gactacaact acaaactgcc tgatgacttc acaggctgtg tgattgcctg gaacagcaac 1320

aacctggaca gcaaggtggg aggcaactac aactacctct acagactgtt caggaagagc 1380

aacctgaaac catttgagag ggacatcagc acagagattt accaggctgg cagcacacca 1440

tgtaatggag tggagggctt caactgttac tttccactcc aatcctatgg cttccaacca 1500

accaatggag tgggctacca accatacagg gtggtggtgc tgtcctttga actgctccat 1560

gcccctgcca cagtgtgtgg accaaagaag agcaccaacc tggtgaagaa caagtgtgtg 1620

aacttcaact tcaatggact gacaggcaca ggagtgctga cagagagcaa caagaagttc 1680

ctgccattcc aacagtttgg cagggacatt gctgacacca cagatgctgt gagggaccca 1740

cagaccttgg agattctgga catcacacca tgttcctttg gaggagtgtc tgtgattaca 1800

cctggcacca acaccagcaa ccaggtggct gtgctctacc aggatgtgaa ctgtactgag 1860

gtgcctgtgg ctatccatgc tgaccaactt acaccaacct ggagggtcta cagcacaggc 1920

agcaatgtgt tccagaccag ggctggctgt ctgattggag cagagcatgt gaacaactcc 1980

tatgagtgtg acatcccaat tggagcaggc atctgtgcct cctaccagac ccagaccaac 2040

agcccaagga gggcaaggtc tgtggcaagc cagagcatca ttgcctacac aatgagtctg 2100

ggagcagaga actctgtggc ttacagcaac aacagcattg ccatcccaac caacttcacc 2160

atctctgtga ccacagagat tctgcctgtg agtatgacca agacctctgt ggactgtaca 2220

atgtatatct gtggagacag cacagagtgt agcaacctgc tgctccaata tggctccttc 2280

tgtacccaac ttaacagggc tctgacaggc attgctgtgg aacaggacaa gaacacccag 2340

gaggtgtttg cccaggtgaa gcagatttac aagacacctc caatcaagga ctttggaggc 2400

ttcaacttca gccagattct gcctgaccca agcaagccaa gcaagaggtc cttcattgag 2460

gacctgctgt tcaacaaggt gaccctggct gatgctggct tcatcaagca atatggagac 2520

tgtctgggag acattgctgc cagggacctg atttgtgccc agaagttcaa tggactgaca 2580

gtgctgcctc cactgctgac agatgagatg attgcccaat acacctctgc cctgctggct 2640

ggcaccatca cctctggctg gacctttgga gcaggagcag ccctccaaat cccatttgct 2700

atgcagatgg cttacaggtt caatggcatt ggagtgaccc agaatgtgct ctatgagaac 2760

cagaaactga ttgccaacca gttcaactct gccattggca agattcagga ctccctgtcc 2820

agcacagcct ctgccctggg caaactccaa gatgtggtga accagaatgc ccaggctctg 2880

aacaccctgg tgaagcaact ttccagcaac tttggagcca tctcctctgt gctgaatgac 2940

atcctgagca gactggacaa ggtggaggct gaggtccaga ttgacagact gattacaggc 3000

agactccaat ccctccaaac ctatgtgacc caacaactta tcagggctgc tgagattagg 3060

gcatctgcca acctggctgc caccaagatg agtgagtgtg tgctgggaca aagcaagagg 3120

gtggacttct gtggcaaggg ctaccacctg atgagttttc cacagtctgc ccctcatgga 3180

gtggtgttcc tgcatgtgac ctatgtgcct gcccaggaga agaacttcac cacagcccct 3240

gccatctgcc atgatggcaa ggctcacttt ccaagggagg gagtgtttgt gagcaatggc 3300

acccactggt ttgtgaccca gaggaacttc tatgaaccac agattatcac cacagacaac 3360

acctttgtgt ctggcaactg tgatgtggtg attggcattg tgaacaacac agtctatgac 3420

ccactccaac ctgaactgga ctccttcaag gaggaactgg acaaatactt caagaaccac 3480

accagccctg atgtggacct gggagacatc tctggcatca atgcctctgt ggtgaacatc 3540

cagaaggaga ttgacagact gaatgaggtg gctaagaacc tgaatgagtc cctgattgac 3600

ctccaagaac tgggcaaata tgaacaatac atcaagtggc catggtacat ctggctgggc 3660

ttcattgctg gactgattgc cattgtgatg gtgaccataa tgctgtgttg tatgacctcc 3720

tgttgttcct gtctgaaagg ctgttgttcc tgtggctcct gttgttaa 3768

<210> 2

<211> 1659

<212> DNA

<213> Artificial sequence

<400> 2

gccaccatgg aagacgccaa aaacataaag aaaggcccgg cgccattcta tcctctagag 60

gatggaaccg ctggagagca actgcataag gctatgaaga gatacgccct ggttcctgga 120

acaattgctt ttacagatgc acatatcgag gtgaacatca cgtacgcgga atacttcgaa 180

atgtccgttc ggttggcaga agctatgaaa cgatatgggc tgaatacaaa tcacagaatc 240

gtcgtatgca gtgaaaactc tcttcaattc tttatgccgg tgttgggcgc gttatttatc 300

ggagttgcag ttgcgcccgc gaacgacatt tataatgaac gtgaattgct caacagtatg 360

aacatttcgc agcctaccgt agtgtttgtt tccaaaaagg ggttgcaaaa aattttgaac 420

gtgcaaaaaa aattaccaat aatccagaaa attattatca tggattctaa aacggattac 480

cagggatttc agtcgatgta cacgttcgtc acatctcatc tacctcccgg ttttaatgaa 540

tacgattttg taccagagtc ctttgatcgt gacaaaacaa ttgcactgat aatgaattcc 600

tctggatcta ctgggttacc taagggtgtg gcccttccgc atagaactgc ctgcgtcaga 660

ttctcgcatg ccagagatcc tatttttggc aatcaaatca ttccggatac tgcgatttta 720

agtgttgttc cattccatca cggttttgga atgtttacta cactcggata tttgatatgt 780

ggatttcgag tcgtcttaat gtatagattt gaagaagagc tgtttttacg atcccttcag 840

gattacaaaa ttcaaagtgc gttgctagta ccaaccctat tttcattctt cgccaaaagc 900

actctgattg acaaatacga tttatctaat ttacacgaaa ttgcttctgg gggcgcacct 960

ctttcgaaag aagtcgggga agcggttgca aaacgcttcc atcttccagg gatacgacaa 1020

ggatatgggc tcactgagac tacatcagct attctgatta cacccgaggg ggatgataaa 1080

ccgggcgcgg tcggtaaagt tgttccattt tttgaagcga aggttgtgga tctggatacc 1140

gggaaaacgc tgggcgttaa tcagagaggc gaattatgtg tcagaggacc tatgattatg 1200

tccggttatg taaacaatcc ggaagcgacc aacgccttga ttgacaagga tggatggcta 1260

cattctggag acatagctta ctgggacgaa gacgaacact tcttcatagt tgaccgcttg 1320

aagtctttaa ttaaatacaa aggatatcag gtggcccccg ctgaattgga atcgatattg 1380

ttacaacacc ccaacatctt cgacgcgggc gtggcaggtc ttcccgacga tgacgccggt 1440

gaacttcccg ccgccgttgt tgttttggag cacggaaaga cgatgacgga aaaagagatc 1500

gtggattacg tcgccagtca agtaacaacc gcgaaaaagt tgcgcggagg agttgtgttt 1560

gtggacgaag taccgaaagg tcttaccgga aaactcgacg caagaaaaat cagagagatc 1620

ctcataaagg ccaagaaggg cggaaagtcc aaattgtaa 1659

Claims (10)

1. Use of caffeine, which is (a) and/or (b) and/or (c) and/or (d) and/or (e) below:

(a) use of caffeine in the manufacture of a product for the treatment of a disease caused by a coronavirus or a coronavirus infection;

(b) use of caffeine in the preparation of a product for the prevention of a disease caused by a coronavirus or a coronavirus infection;

(c) the application of caffeine in preparing products for inhibiting susceptibility of coronavirus;

(d) use of caffeine in the manufacture of a product for reducing the risk of coronavirus infection;

(e) use of caffeine in the preparation of a coronavirus inhibitor.

2. Use according to claim 1, characterized in that: the product is a medicament or pharmaceutical formulation.

3. Use according to claim 1 or 2, characterized in that: the coronavirus is a beta genus coronavirus.

4. Use according to claim 3, characterized in that: the coronavirus is SARS-CoV-2.

5. A medicine or pharmaceutical composition comprises caffeine as active ingredient;

the medicament or the medicament composition has at least one of the following effects:

1) treating a disease caused by a coronavirus or a coronavirus infection;

2) preventing disease caused by coronavirus or coronavirus infection;

3) inhibiting susceptibility to coronavirus;

4) reducing the risk of coronavirus infection

5) A coronavirus inhibitor.

6. The drug or pharmaceutical composition of claim 5, wherein: the coronavirus is a beta genus coronavirus; the coronavirus is specifically selected from SARS-CoV-2.

7. A method of inhibiting infection of an animal by a coronavirus comprising the steps of: caffeine is administered to the recipient animal to inhibit infection of the animal by the coronavirus.

8. A method for preventing a disease caused by coronavirus, comprising the steps of: the administration of caffeine to a recipient animal is useful for preventing a disease caused by coronavirus.

9. A method of treating a disease caused by a coronavirus, comprising the steps of: the subject animals are administered caffeine to treat a disease caused by coronavirus.

10. The method according to any one of claims 7-9, wherein: the coronavirus is a beta genus coronavirus; the coronavirus is specifically selected from SARS-CoV-2.

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