WO2023093708A1 - Anti-syncytial virus membrane fusion inhibitor - Google Patents

Abstract

The present invention relates to the field of medicine synthesis. Disclosed is an anti-syncytial virus (RSV) membrane fusion inhibitor. The anti-syncytial virus membrane fusion inhibitor of the present invention is used for preparing a pharmaceutical composition for treating diseases. Also disclosed is a use of the pharmaceutical composition in preparation for a drug for treating syncytial virus pneumonia.

Description

An anti-syncytial virus membrane fusion inhibitor

This application claims the priority of the Chinese patent application with the application number 202111403215.4 and the invention title "An Anti-Syncytial Virus Membrane Fusion Inhibitor" submitted to the China Patent Office on November 24, 2021, the entire contents of which are incorporated herein by reference In this application.

technical field

The invention relates to the field of biotechnology, in particular to an anti-syncytial virus membrane fusion inhibitor.

Background technique

Human respiratory syncytial virus (RSV) is widely distributed all over the world and is an important viral pathogen that causes lower respiratory tract infection. RSV infection can lead to high rates of hospitalization and mortality in infants, the elderly, and immunocompromised populations worldwide. About 70% of infants are infected with RSV within one year after birth, and the vast majority of children will be infected within two years after birth. 1/3 of infants and young children who die due to acute lower respiratory tract infection are caused by RSV infection. The World Health Organization (WHO) reports that about 64 million children are infected with RSV worldwide each year, and nearly 3.5 million children are hospitalized due to severe RSV infection, which is 16 times that of influenza. Death from RSV infection is a major cause of hospitalization and death in children worldwide. In the United States, 20% to 25% of infant pneumonia and 50% to 75% of bronchiolitis are caused by RSV. A study from South Korea showed that the 20-day all-cause mortality rate of RSV-infected patients over the age of 18 was higher than that of influenza (18.4% vs. 6.7%); compared with the seasonal influenza group, the risk of death caused by RSV infection was significantly lower. high. In Beijing, 48% of viral pneumonia and 58% of bronchiolitis were caused by RSV (1980-1984); in Guangzhou, 31.4% of children's pneumonia and bronchiolitis were caused by RSV (1973-1986). The data of WHO also shows that there are nearly 30 million cases of elderly patients with RSV infection worldwide every year, and at least 2 million cases are severe hospitalized patients. Statistics show that RSV infection accounts for 20% of the deaths among the elderly over 65 years old. According to the latest epidemiological survey results, there are about 487,247 people requiring medical treatment, 17,799 hospitalizations and 8,482 deaths in each RSV epidemic season among adults over the age of 18 in the UK alone. 36% of medical treatment, 79% of hospitalization, and 93% of death. China currently has more than 240 million people over the age of 60, all of whom belong to the high-risk group of RSV infection, and the burden faced by families and society is huge. Because there is still no effective vaccine for preventing RSV infection and effective drugs for treating RSV infection in the world, it has brought a great burden to the health care systems of countries all over the world.

The scientific research team of the present invention has been committed to the research and development of viral membrane fusion inhibitor drugs, and has developed a series of polypeptide membrane fusion inhibitors with strong inhibitory activity against syncytial virus (RSV), and they can also effectively inhibit RSV. Infection, see Chinese patent CN202010108065.3 for details, because the purpose of this invention patent is to provide a lead compound for the further development of RSV therapeutic drugs. At the same time, the patented compound has high gelation characteristics, and is extremely difficult to dissolve in water and has poor druggability. The purpose of the present invention is to further develop an anti-human respiratory syncytial virus (RSV) membrane fusion inhibitor with good solubility, weak gelation properties and good druggability on the basis of the above-mentioned patents, in order to meet clinical needs.

Contents of the invention

In view of this, the present invention provides an anti-syncytial virus membrane fusion inhibitor.

In order to achieve the above-mentioned purpose of the invention, the present invention provides the following technical solutions:

The invention provides a kind of compound, described compound comprises:

(I), having an amino acid sequence as shown in formula I; or

Ac-Ile-Glu-Gln-Val-Asn-Lys-Lys-Ile-Glu-Gln-Ser-Leu-

Lys-Phe-Ile-Glu-Lys-Ser-Asp-Lys-Leu-Leu-Glu-Asn-Val-

Asn-Lys-Gly-(AA1)n-AA2(R)-AA3

Formula I

AA1 in formula I is selected from Lys, Dap, Dab, Orn, Dah, Dao, Asp, Glu, Ada, Apm, or Asu;

AA2 in formula I is selected from Lys, Dap, Dab, Orn, Dah, Dao, Asp[NH(CH ₂ ) _m NH], Glu[NH(CH ₂ ) _m NH], Ada[NH(CH ₂ ) _m NH] ], Apm[NH(CH ₂ ) _m NH], or Asu[NH(CH ₂ ) _m NH];

Said m comprises a natural integer;

AA3 in formula I includes _NH or OH;

n in formula I includes natural integers;

R in formula I is selected from cholesteryl succinate, 2-cholesterol acetate, 2-cholesterol propionate, 2-cholesterol butyrate, 2-cholesterol isobutyrate, 2-cholesterol valerate, 2-cholesterol isovalerate , or 2-cholesteryl caproic acid;

(II), a sequence having one or more amino acids substituted, deleted, added and/or replaced on the basis of the amino acid sequence shown in (I); or

(III), a sequence having more than 90% homology with the amino acid sequence shown in (I); or

(IV), a pharmaceutically acceptable salt, solvate, chelate or non-covalent complex formed by the compound shown in formula I; and/or

(V), a prodrug based on the compound shown in formula I; and/or

(VI), including any mixture of (I), (II), (III), (IV) and/or (V).

In some specific implementation methods, in the compound, the m is selected from an integer of 2 to 10; the n is selected from an integer of 1 to 10.

In the present invention, when there is a discrepancy or doubt between the chemical structural formula and the chemical name of a compound, the chemical structural formula shall be used to precisely define the compound. The compounds described in the present invention may contain one or more chiral centers, and/or double bonds and such structures, and the isomers of the compounds are also within the protection scope of the present invention. The compounds may exist as stereoisomers, including double bond isomers (such as geometric isomers), optical enantiomers or diastereomers. Correspondingly, any chemical structure within the scope of the description of the present invention, whether it contains the above-mentioned similar structures in part or in the whole structure, all possible enantiomers and diastereoisomers of this compound are included, wherein also Included are individual stereoisomers (such as individual geometric isomers, individual enantiomers or individual diastereomers) as well as any mixtures of such isomers. These mixtures of racemic isomers and stereoisomers can also be further resolved into enantiomers or stereoisomers of their constituents by those skilled in the art using continuous separation techniques or chiral molecular synthesis methods body.

The present invention also provides a preparation method of the compound, which includes the following steps:

Step 1, the solid-phase peptide synthesis method prepares the peptide resin;

Step 2, acid hydrolysis and purification to obtain the compound.

The present invention also provides the application of the compound and/or the compound prepared by the preparation method in the preparation of medicine or medicine combination for preventing and/or treating diseases.

The present invention also provides the application of said compound and/or the compound prepared by said preparation method in the preparation of medicine or medicine combination for preventing and/or treating pneumonia.

The present invention also provides the application of the compound and/or the compound prepared by the preparation method in the preparation of medicine or medicine combination for preventing and/or treating syncytial virus pneumonia.

In some embodiments, the compound has syncytial virus inhibitory activity in vitro.

The present invention also provides a medicine, including the compound and/or the compound prepared by the preparation method and acceptable adjuvants and/or assistants.

The dosage form of the medicine includes one or more of oral preparations, injections, drops or external preparations for skin.

The present invention also provides a pharmaceutical combination, including any of the following items and any other active ingredients;

(I), said compound; and/or

(II), the compound obtained by the preparation method; and/or

(III), the drug.

The other arbitrary active ingredients include those that assist the compound or the drug to strengthen the treatment of diseases or symptoms, or that have a therapeutic effect on concurrent diseases or syndromes.

The present invention also provides a method for preventing and/or treating syncytial virus pneumonia, which comprises administering any of the following items to a subject:

(I), said compound; and/or

(II), the compound obtained by the preparation method; and/or

(III), the drug; and/or

(IV), the drug combination.

The method for preventing and/or treating syncytial virus pneumonia includes different administration methods such as oral administration and injection.

Detailed ways

The invention discloses an anti-syncytial virus membrane fusion inhibitor, and those skilled in the art can learn from the content of this article and appropriately improve the process parameters to realize it. In particular, it should be pointed out that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and the relevant personnel can obviously make changes or appropriate changes and combinations to the method and application described herein without departing from the content, spirit and scope of the present invention to realize and Apply the technology of the present invention.

The present invention firstly provides a compound represented by formula I, the pharmaceutically acceptable salt, solvate, chelate or non-covalent complex formed by the compound, the prodrug based on the compound, or the above-mentioned Any mixture of forms.

Ac-Ile-Glu-Gln-Val-Asn-Lys-Lys-Ile-Glu-Gln-Ser-Leu-

Lys-Phe-Ile-Glu-Lys-Ser-Asp-Lys-Leu-Leu-Glu-Asn-Val-

Asn-Lys-Gly-(AA1)n-AA2(R)-AA3

Formula I

AA1 in formula I is Lys, or Dap, or Dab, or Orn, or Dah, or Dao, or Asp, or Glu, or Ada, or Apm, or Asu;

AA2 in formula I is Lys, or Dap, or Dab, or Orn, or Dah, or Dao, or

Asp[NH(CH ₂ ) _m NH], or Glu[NH(CH ₂ ) _m NH], or Ada[NH(CH ₂ ) _m NH], or Apm[NH(CH ₂ ) _m NH] , or Asu[NH(CH ₂ ) _m NH];

Where: m is an integer from 2 to 10;

AA3 in formula I is NH ₂ , or OH;

n in formula I is an integer from 1 to 10;

R in formula I is cholesteryl succinate, or 2-cholesterol acetate, or 2-cholesterol propionate, or 2-cholesterol butyrate, or 2-cholesterol isobutyrate, or 2-cholesterol Valeric acid, or 2-cholesterol isovaleric acid, or 2-cholesteryl hexanoic acid.

The present invention also provides a pharmaceutical combination comprising the compound according to the present invention, and the use of the pharmaceutical combination of the compound of the present invention for preparing a medicine for treating diseases.

Preferably, the use of the drug combination in the preparation of drugs for the treatment of syncytial virus pneumonia.

More contents involved in the present invention are described in detail below, or some of them can also be realized in the embodiments of the present invention.

Unless otherwise specified, the quantities and reaction conditions used herein to express different components can be interpreted as "approximately" or "approximately" in any case. Correspondingly, unless otherwise specified, the numerical parameters cited below and in the claims are approximate parameters, and different numerical parameters may be obtained due to different standard errors under respective experimental conditions.

In this paper, when there is a discrepancy or doubt between the chemical structural formula and the chemical name of a compound, the chemical structural formula is used to define the compound exactly. The compounds described herein may contain one or more chiral centers, and/or double bonds and the like, and may also exist as stereoisomers, including double bond isomers (such as geometric isomers), optically active Enantiomers or diastereomers. Correspondingly, any chemical structure within the scope of the description herein, whether it contains the above-mentioned similar structures in part or in the whole structure, includes all possible enantiomers and diastereoisomers of this compound, including Any single stereoisomer (such as a single geometric isomer, a single enantiomer or a single diastereoisomer) and any mixture of these isomers are contemplated. These mixtures of racemic isomers and stereoisomers can also be further resolved into enantiomers or stereoisomers of their constituents by those skilled in the art using continuous separation techniques or chiral molecular synthesis methods body.

Compounds of formula I include, but are not limited to, optical isomers, racemates and/or other mixtures of these compounds. In the above cases, a single enantiomer or diastereoisomer, such as an optically active isomer, can be obtained by asymmetric synthesis or racemate resolution. The resolution of the racemate can be achieved by different methods, such as conventional recrystallization with resolution aids, or chromatography. In addition, the compounds of formula I also include cis and/or trans isomers with double bonds.

The compounds of the present invention include, but are not limited to, compounds represented by formula I and all their different pharmaceutically usable forms. Various pharmaceutically acceptable forms of these compounds include various pharmaceutically acceptable salts, solvates, complexes, chelates, non-covalent complexes, prodrugs based on the above-mentioned substances and combinations of the above-mentioned forms. any mixture.

The above-mentioned prodrugs include ester or amide derivatives of the compound shown in formula I contained in the compound.

The compound represented by the formula I provided by the invention is stable in property, is a novel anti-syncytial virus membrane fusion inhibitor, and can be used for the treatment of syncytial virus pneumonia.

The preparation method of the present invention comprises: adopting the solid-phase polypeptide synthesis method to prepare the peptide resin, and the peptide resin is subjected to acid hydrolysis to obtain a crude product, and finally the crude product is purified to obtain a pure product; wherein the step of preparing the peptide resin by the solid-phase polypeptide synthesis method is on the carrier resin The corresponding protected amino acids or fragments in the polypeptide sequence are sequentially inserted into the peptide resin by solid-phase coupling synthesis.

In the above preparation method, the amount of the Fmoc-protected amino acid or protected amino acid fragment is 1.2-6 times of the total moles of the resin fed; preferably 2.5-3.5 times.

In the above preparation method, the substitution value of the carrier resin is 0.2-1.0 mmol/g resin, preferably 0.3-0.5 mmol/g resin.

As a preferred solution of the present invention, the solid-phase coupling synthesis method is as follows: the protected amino acid-resin obtained in the previous step reaction removes the Fmoc protecting group and then reacts with the next protected amino acid for coupling reaction. The deprotection time for the de-Fmoc protection is 10-60 minutes, preferably 15-25 minutes. The coupling reaction time is 60-300 minutes, preferably 100-140 minutes.

The coupling reaction needs to add a condensation reagent, and the condensation reagent is selected from DIC (N,N-diisopropylcarbodiimide), N,N-dicyclohexylcarbodiimide, benzotriazole hexafluorophosphate -1-yl-oxytripyrrolidinylphosphonium, 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate , Benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate or O-benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoro One of borates; preferred is N,N-diisopropylcarbodiimide. The molar dosage of the condensation reagent is 1.2-6 times, preferably 2.5-3.5 times, the total molar number of amino groups in the amino resin.

The coupling reaction requires the addition of an activating reagent selected from 1-hydroxybenzotriazole or N-hydroxy-7-azabenzotriazole, preferably 1-hydroxybenzotriazole. The dosage of the activating agent is 1.2 to 6 times, preferably 2.5 to 3.5 times, the total moles of amino groups in the amino resin.

As a preferred solution of the present invention, the reagent for removing Fmoc protection is a PIP/DMF (piperidine/N,N-dimethylformamide) mixed solution, and the mixed solution contains 10-30% of piperidine (V ). The dosage of the de-Fmoc protection reagent is 5-15 mL per gram of amino resin, preferably 8-12 mL per gram of amino resin.

Preferably, the peptide resin is subjected to acid hydrolysis to simultaneously remove the resin and side chain protecting groups to obtain the crude product:

Further preferably, the acidolysis agent used during acidolysis of the peptide resin is a mixed solvent of trifluoroacetic acid (TFA), 1,2-ethanedithiol (EDT) and water, and the volume ratio of the mixed solvent is: TFA 80-95%, EDT 1-10%, and the balance is water.

More preferably, the volume ratio of the mixed solvent is: TFA is 89-91%, EDT is 4-6%, and the balance is water. Optimally, the volume ratio of the mixed solvent is: TFA is 90%, EDT is 5%, and the balance is water.

The dosage of the acidolysis agent is 4-15mL of acidolysis agent per gram of peptide resin; preferably, 7-10mL of acidolysis agent is required per gram of peptide resin.

The time for cleavage using an acidolysis agent is 1-6 hours at room temperature, preferably 3-4 hours.

Further, the crude product was purified by high performance liquid chromatography and freeze-dried to obtain the pure product, the specific method is:

Take the crude product, stir it with water, adjust the pH value until it is completely dissolved, filter the solution with a 0.45 μm mixed microporous membrane, and purify it for later use;

Adopt high-performance liquid chromatography to carry out purification, the chromatographic filling material for purification is the reverse phase C18 of 10 μ m, mobile phase system is 0.1% TFA/water solution-0.1% TFA/acetonitrile solution, the chromatographic column flow rate of 77mm * 250mm is 90mL/min (can be Use chromatographic columns of different specifications for purification; according to different specifications of chromatographic columns, adjust the corresponding flow rate), use a gradient system for elution, cycle sample purification, take the crude product solution and load it on the chromatographic column, start the mobile phase elution, After collecting the main peak and evaporating acetonitrile, the concentrated solution of the purified intermediate was obtained;

Take the concentrated solution of the purified intermediate and filter it with a 0.45 μm filter membrane for later use;

Use high performance liquid chromatography to change salt, the mobile phase system is 1% acetic acid/water solution-acetonitrile, the chromatographic filler for purification is 10 μm reverse phase C18, and the flow rate of the 77mm×250mm chromatographic column is 90mL/min (different specifications can be used) The chromatographic column is purified; the corresponding flow rate can be adjusted according to different specifications of the chromatographic column); the gradient elution is used, and the cycle loading method is used to load the sample into the chromatographic column, start the mobile phase elution, collect the spectrum, and observe the change of the absorbance , collect the salt-changing main peak and use the analytical liquid phase to detect the purity, combine the salt-changing main peak solutions, concentrate under reduced pressure, and obtain the pure acetic acid aqueous solution, and obtain the pure product after freeze-drying.

The Chinese names corresponding to the English abbreviations involved in the present invention are shown in Table 1:

Table 1 Comparison of Chinese and English abbreviations

The raw materials and reagents used in the anti-syncytial virus membrane fusion inhibitor provided by the present invention can be purchased from the market.

Below in conjunction with embodiment, further set forth the present invention:

The preparation of embodiment 1 compound

1. Synthesis of peptide resin

Using Rink Amide BHHA resin as the carrier resin, through de-Fmoc protection and coupling reaction, sequentially coupled with the protected amino acids corresponding to the polypeptide sequence to prepare the peptide resin.

(1) Access to the first protected amino acid in the main chain

Take 0.03 mol of the first protected amino acid and 0.03 mol HOBt, and dissolve them with an appropriate amount of DMF; take another 0.03 mol of DIC, slowly add it to the protected amino acid DMF solution under stirring, and stir and react at room temperature for 30 minutes to obtain the activated protected amino acid. Amino acid solution, spare.

Take 0.01mol Rink amide MBHA resin (substitution value about 0.4mmol/g), use 20% PIP/DMF solution to deprotect for 25 minutes, wash and filter to obtain Fmoc-free resin.

Add the activated first protected amino acid solution to the resin from which Fmoc has been removed, perform a coupling reaction for 60-300 minutes, filter and wash to obtain a resin containing one protected amino acid.

(2) Access to the main chain to protect amino acids

Using the same method as above for inserting the first protected amino acid in the main chain, sequentially insert the above-mentioned corresponding protected amino acids in the polypeptide sequence to obtain a peptide resin.

(3) Access to side chains

Take 0.02mol cholesteryl succinate and 0.02mol HOBt, and dissolve them in an appropriate amount of DMF; take another 0.02mol DIC, slowly add them to the DMF solution of amino acids under stirring, and react at room temperature for 30 minutes.

Take 2.5mmol tetrakistriphenylphosphine palladium and 25mmol phenylsilane, dissolve them with an appropriate amount of dichloromethane, put them into the resin containing the main chain amino acid, stir for 4 hours to remove the protection, filter and wash, and obtain the de-Alloc resin for later use.

The activated cholesteryl succinate monoester solution is added to the resin that has been de-Alloced, the coupling reaction takes 60 to 300 minutes, and the peptide resin is obtained by filtering, washing and drying.

2. Preparation of crude product

Take the above peptide resin, add a lysis reagent with a volume ratio of TFA:water:EDT=95:5:5 (lysis reagent 10mL/g resin), stir evenly, stir and react at room temperature for 3 hours, use a sand core funnel to filter the reaction mixture, collect The filtrate and resin were washed 3 times with a small amount of TFA, the combined filtrates were concentrated under reduced pressure, anhydrous ether was added to precipitate, and then the precipitate was washed 3 times with anhydrous ether, and the off-white powder was obtained as the crude product after draining.

3. Preparation of pure product

Take the above crude product, add water and stir to dissolve, filter the solution with a 0.45 μm mixed microporous membrane, and purify it for later use. High performance liquid chromatography is used for purification, the chromatographic filler for purification is 10 μm reversed-phase C18, the mobile phase system is 0.1% TFA/water solution-0.1% TFA/acetonitrile solution, and the flow rate of a 30mm×250mm chromatographic column is 20mL/min. Gradient system elution, cyclic sample injection and purification, take the crude product solution and load it on the chromatographic column, start the mobile phase elution, collect the main peak and evaporate the acetonitrile to obtain the concentrated solution of the purified intermediate;

The concentrated solution of the purified intermediate is filtered with a 0.45 μm filter membrane for later use, and the salt is replaced by high performance liquid chromatography. The mobile phase system is 1% acetic acid/water solution-acetonitrile, and the chromatographic filler for purification is 10 μm reversed-phase C18, 30mm×250mm The flow rate of the chromatographic column is 20mL/min (the corresponding flow rate can be adjusted according to different specifications of the chromatographic column); gradient elution is adopted, and the method of cyclic loading is used to load the sample into the chromatographic column, start the mobile phase elution, collect the spectrum, and observe According to the change of absorbance, the main peak of salt-changing was collected and the purity was detected by analytical liquid phase, the solution of the main peak of salt-changing was combined, concentrated under reduced pressure to obtain pure acetic acid aqueous solution, and freeze-dried to obtain pure peptide.

Synthesized the lipopeptide compound shown in table 2 with the above method:

Table 2 Sequence structure of lipopeptide compounds

The mensuration of embodiment 2 solubility

The measurement results are shown in Table 3:

Table 3 Solubility of Compounds

The determination of embodiment 3 in vitro antiviral activity

The antiviral activity of the novel RSV fusion inhibitor was further evaluated using luciferase-based reporter tagged RSV virus (RSV-luc).

Dilute the peptide drug in a 3-fold gradient in a 96-well plate, with 3 replicate wells for each peptide, 9 dilution gradients, with a final volume of 50 μL/well, and then add 50 μL (100 TCID ₅₀ ) RSV to the 96-well plate containing the polypeptide drug -luc virus solution, incubate at room temperature for 1 h. Prepare a Hep-2 cell suspension with a concentration of 10×10 ⁴ /mL in DMEM medium, mix well and add to the above-mentioned 96-well plate, 100 μL/well. After culturing in a 37°C 5% CO ₂ cell incubator for 48 hours, discard the supernatant, pat dry on clean absorbent paper, add 30 μL/well of cell lysate, and use Bright-Glo Luciferase Assay reagent after lysis for 15 minutes (Promega) to measure relative fluorescence units (RLU) per well. Finally, Graphpad software was used to process the obtained data, and the IC ₅₀ value of each polypeptide drug was calculated. The experimental results are shown in Table 4.

The inhibitory activity of table 4 compound to RSV-Luc

An anti-syncytial virus membrane fusion inhibitor provided by the present invention has been introduced in detail above. This article uses specific examples to illustrate the principle and implementation of the present invention. The description of the above embodiments is only used to help understand the method and core idea of the present invention. It should be pointed out that for those skilled in the art, without departing from the principles of the present invention, some improvements and modifications can be made to the present invention, and these improvements and modifications also fall within the protection scope of the claims of the present invention.

Claims (9)

1. A compound characterized in that it comprises:

   (I), having an amino acid sequence as shown in formula I; or

   Ac-Ile-Glu-Gln-Val-Asn-Lys-Lys-Ile-Glu-Gln-Ser-Leu-

   Lys-Phe-Ile-Glu-Lys-Ser-Asp-Lys-Leu-Leu-Glu-Asn-Val-

   Asn-Lys-Gly-(AA1)n-AA2(R)-AA3

   Formula I

   AA1 in formula I is selected from Lys, Dap, Dab, Orn, Dah, Dao, Asp, Glu, Ada, Apm, or Asu;

   AA2 in formula I is selected from Lys, Dap, Dab, Orn, Dah, Dao, Asp[NH(CH ₂ ) _m NH], Glu[NH(CH ₂ ) _m NH], Ada[NH(CH ₂ ) _m NH] ], Apm[NH(CH ₂ ) _m NH], or Asu[NH(CH ₂ ) _m NH];

   Said m comprises a natural integer;

   AA3 in formula I includes _NH or OH;

   n in formula I includes natural integers;

   R in formula I is selected from cholesteryl succinate, 2-cholesterol acetate, 2-cholesterol propionate, 2-cholesterol butyrate, 2-cholesterol isobutyrate, 2-cholesterol valerate, 2-cholesterol isovalerate , or 2-cholesteryl caproic acid;

   (II), a sequence having one or more amino acids substituted, deleted, added and/or substituted on the basis of the amino acid sequence shown in (I); or

   (III), a sequence having more than 90% homology with the amino acid sequence shown in (I); or

   (IV), a pharmaceutically acceptable salt, solvate, chelate or non-covalent complex formed by the compound shown in formula I; and/or

   (V), a prodrug based on the compound shown in formula I; and/or

   (VI), including any mixture of (I), (II), (III), (IV) and/or (V).
2. The compound of claim 1, wherein,

   The m is an integer selected from 2 to 10;

   The n is an integer selected from 1 to 10.
3. The preparation method of the compound as described in any one of claims 1 and 2, is characterized in that, comprises the steps:

   Step 1, the solid-phase peptide synthesis method prepares the peptide resin;

   Step 2, acid hydrolysis and purification to obtain the compound.
4. Application of any of the following items in the preparation of drugs or drug combinations for the prevention and/or treatment of diseases:

   (1), the compound as claimed in claim 1 or 2; And/or

   (II), the compound that preparation method prepares as claimed in claim 3.
5. Application of any of the following items in the preparation of a drug or drug combination for the prevention and/or treatment of pneumonia:

   (1), the compound as claimed in claim 1 or 2; And/or

   (II), the compound that preparation method prepares as claimed in claim 3.
6. Application of any of the following items in the preparation of drugs or drug combinations for the prevention and/or treatment of syncytial virus pneumonia:

   (1), the compound as claimed in claim 1 or 2; And/or

   (II), the compound that preparation method prepares as claimed in claim 3.
7. The medicine is characterized in that it comprises the compound according to claim 1 or 2 and/or the compound prepared by the preparation method according to claim 3, and acceptable adjuvants and/or auxiliary agents.
8. The drug combination is characterized in that it includes any of the following items and any other active ingredients;

   (1), the compound as claimed in claim 1 or 2; And/or

   (II), the compound prepared by the preparation method as claimed in claim 3; and/or

   (III), the medicine as claimed in claim 7.
9. A method for preventing and/or treating syncytial virus pneumonia, characterized in that it comprises administering any of the following to a subject:

   (1), the compound as claimed in claim 1 or 2; And/or

   (II), the compound obtained by the preparation method as claimed in claim 3; and/or

   (III), the medicine as claimed in claim 7; and/or

   (IV), the pharmaceutical combination as claimed in claim 8.