CN115400121A

CN115400121A - Application of SNX-2112 in preparation of medicine for resisting adenovirus infection

Info

Publication number: CN115400121A
Application number: CN202210503360.8A
Authority: CN
Inventors: 吴建国; 陈绪林; 刘敏丽; 万品; 杨戈
Original assignee: Foshan Institute Of Pathogenic Microorganisms
Current assignee: Foshan Institute Of Pathogenic Microorganisms
Priority date: 2022-04-29
Filing date: 2022-05-09
Publication date: 2022-11-29
Anticipated expiration: 2042-05-09
Also published as: CN115400121B

Abstract

The invention belongs to the technical field of biomedicine, and discloses application of SNX-2112 in preparing a medicament for resisting adenovirus infection, wherein the medicament for relieving and/or preventing and/or treating the adenovirus infection acts by inhibiting the activity of adenovirus replication. The adenovirus is various adenovirus types including but not limited to AdV3 subtype, adV5 subtype. A medicament for ameliorating and/or preventing and/or treating an adenoviral infection comprises SNX-2112 and a pharmaceutically acceptable carrier. The invention provides application of a small molecular compound SNX-2112 in preparing a medicament for treating adenovirus infection, and provides a safe and effective small molecular compound for treating adenovirus clinically. SNX-2112 can effectively inhibit the replication of adenovirus in a nontoxic range, can be further developed into a medicament for treating diseases caused by adenovirus infection, and has wide application prospect.

Description

Application of SNX-2112 in preparation of medicine for resisting adenovirus infection

Technical Field

The invention belongs to the technical field of biomedicine, and particularly relates to application of SNX-2112 in preparation of a medicament for resisting adenovirus infection.

Background

Currently, human adenoviruses (HAdV) belong to the genus mammalian adenoviruses of the family adenoviridae. Adenovirus is a nonenveloped icosahedral nucleocapsid DNA virus, the core of the viral genome is a linear double-stranded DNA molecule of about 36kb, and its genome is highly densely packed and organized into chromatin by hundreds of histone-like protein VII and protamine-like protein Mu (also known as protein X). The capsid of adenovirus has 240 hexon proteins (hexon) and the 12 apices of the icosahedral capsid are complexes of pentameric (penton) and trimeric (fiber) proteins. The 12 fiber proteins project from the capsid surface with the penton protein as the base, and the top of the fiber forms the knob region (knob). The knob region of the penton protein and the fiber protein can be combined with a virus receptor on the cell surface, and plays an important role in the process of infecting cells by the virus. The smaller capsid proteins IIIa, VI, VIII and IX are embedded in the capsid, wherein capsid protein VI is located on the inner surface of the capsid and connects the capsid to the core comprising the viral genome via capsid protein V. Also a small amount of capsid protein IVa2 is involved in genome packaging and adenovirus protease (AVP) formation in the capsid.

Adenovirus infection can occur in any season, but often winter and early spring are the peak seasons of viral infection. Based on serum neutralization, hemagglutination epitope, genome sequence and function, human adenoviruses are divided into seven types, a, B, C, D, E, F and G, and 57 serotypes are provided. The types of adenovirus popular in China mainly include type 1, type 3, type 4, type 5, type 7, type 11, type 14, type 40, type 41 and type 55, wherein adenovirus flow behaviors of type 3 and type 5 are dominant. It was found that various types of adenoviruses, except for the hexon, fiber, penton genes, are highly conserved in the genome and that intraspecies recombination rarely occurs. Therefore, the method is beneficial to overcoming the limitation of the specificity of the medicaments on the type of the adenovirus, and generally, the antiviral medicaments aiming at the later stage of the entry of the adenovirus have broad-spectrum anti-adenovirus activity in the adenovirus species.

Adenovirus infection has a variety of clinical symptoms and disease manifestations, which depend largely on the type of adenovirus, the immune status of the host and the site of infection. Common sites of infection with adenovirus include the respiratory tract, corneal epithelium and intestinal tract. 90% of cases of viral conjunctivitis are caused by adenovirus infection, usually associated with B, D or type E adenovirus infection, and are often present in the hospitalized recruits in the form of pharyngeal conjunctivitis or Epidemic Keratoconjunctivitis (EKC). B. Adenovirus type D or E also often causes acute respiratory disease and viral pneumonia. Two of the more serious consequences of respiratory adenovirus infection are pneumonia, which can be fatal in children. And acute respiratory distress syndrome, which is more common in people who are eligible. Adenoviruses of the A, F and G types are associated with gastrointestinal infections. Adenovirus infection is the primary cause of gastroenteritis in children, second only to norovirus and rotavirus. In general, adenoviruses are susceptible to all populations, with more serious diseases and even death often occurring in infected newborns, children, and immunocompromised populations (hematopoietic stem cells and organ transplant patients).

Currently, there are no approved antiviral drugs for the treatment of adenoviral infections. Certain DNA/RNA synthesis inhibiting antiviral drugs approved for the treatment of other viral infections (e.g., cidofovir, ganciclovir, and ribavirin) have been used clinically to treat severe adenoviral infections by expanding the indications as trial drugs. However, most of these drugs have limited efficacy and severe adverse reactions. Therefore, there is a need to develop other safer and more effective anti-adenovirus drugs.

SNX-2112 (PF-04928473) is a novel and potent HSP90 inhibitor that inhibits the proliferation of a variety of human tumor cell lines. SNX-2112 inhibits the growth of cancer cells by inducing the degradation of associated oncogenic client proteins in tumor cells, leading to the blockade of many key oncogenic pathways. However, no report is currently found on the treatment of adenoviral infection with SNX-2112.

Through the above analysis, the problems and defects of the prior art are as follows:

(1) There are no reports of SNX-2112 treatment for adenovirus infection.

(2) The prior art is related to the medicine for treating adenovirus infection, which has low efficacy and poor effect.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides the application of SNX-2112 in preparing a medicament for resisting adenovirus infection.

The invention is realized by the application of SNX-2112 in preparing a medicament for relieving and/or preventing and/or treating adenovirus infection.

Further, the structural formula of SNX-2112 is as follows:

further, the adenovirus comprises adenovirus type B AdV3 subtype and adenovirus type C AdV5 subtype.

Further, the adenovirus is one or more of

human adenovirus type

1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

Further, the medicament for alleviating and/or preventing and/or treating an adenovirus infection acts by inhibiting the activity of adenovirus replication.

Further, the medicament for alleviating and/or preventing and/or treating adenovirus infection comprises SNX-2112 and a pharmaceutically acceptable carrier.

Furthermore, the dosage form of the medicament for relieving and/or preventing and/or treating the adenovirus infection is any clinically acceptable oral administration dosage form, injection administration dosage form or external administration dosage form.

Further, the medicine for relieving and/or preventing and/or treating the adenovirus infection is tablets, capsules, granules, oral liquid and injection.

The invention also aims to provide application of SNX-2112 in preparing an adenovirus inhibitor.

Aiming at the current situation that the prior art has no antiviral drug for adenovirus infection, the invention provides a novel antiviral drug for adenovirus infection, namely SNX-2112 by combining experimental data of low cytotoxicity in Vero cells, high antiviral activity on two adenoviruses and the like in the research and development process, provides a new technology for the antiviral drug for adenovirus infection, and provides a brand new therapy and more treatment options for treating diseases caused by adenovirus infection.

The invention provides application of a small molecular compound SNX-2112 in preparing a medicament for treating adenovirus infection, and provides a safe and effective small molecular compound for treating adenovirus clinically. SNX-2112 can effectively inhibit the replication of adenovirus in a non-toxic range, can be further developed into a medicament for treating diseases caused by adenovirus infection, and has wide application prospect.

The SNX-2112 of the invention is a small molecule compound which still does not show any cytotoxicity at 5. Mu.M in Vero cells. Thus, CC ₅₀ (half lethal concentration) greater than 5. Mu.M. SNX-2112 is capable of dose-dependent inhibition of viral replication for both adenoviruses (AdV 3 and AdV 5). Their IC for AdV3 in Vero cells ₅₀ (median inhibitory concentration) 0.17. Mu.M only, IC for AdV5 ₅₀ It was 0.33. Mu.M. By calculation, the Selection Index (SI) of SNX-2112 is greater than 10 on both adenoviruses, indicating that SNX-2112 has broad-spectrum activity against adenoviral replication.

Considering the technical scheme as a whole or from the perspective of products, the technical scheme to be protected by the invention has the following technical effects and advantages:

the invention provides a novel anti-adenovirus drug-SNX-2112, which makes up for the technical defect that the prior art has no anti-virus drug aiming at adenovirus infection.

As inventive supplementary proof of the claims of the present invention, also present several important aspects:

(1) The expected income and commercial value after the technical scheme of the invention is converted are as follows: the invention focuses on the field of core treatment by meeting clinical requirements as a guide, and has huge commercial value and expected income after conversion based on clinical value, medicinal economic value and commercial value of products

(2) The technical scheme of the invention fills the technical blank in the industry at home and abroad: the invention provides a new technology of antiviral drugs for adenovirus infection.

Drawings

FIG. 1 shows Vero cells provided by an example of the invention and SNX-2112 at different concentration gradients containing 5% CO at 37 ℃ ₂ Cell viability profile of Vero cells relative to non-drug treated cells measured after 48 hours incubation in the incubator of (a);

FIG. 2 is a graph showing the percentage of inhibition of Vero cells to AdV3 after incubation at 37 ℃ for 48 hours with different drug concentration gradients after adding SNX-2112 with different concentration gradients to Vero cells provided in the example of the present invention, infecting AdV3 with MOI 0.55, and treating the Vero cells with different drug concentration gradients relative to non-drug-added cells after viral infection;

FIG. 3 is a graph showing the percentage of inhibition of AdV5 by Vero cells treated with different drug concentration gradients relative to untreated drug cells after viral infection after incubation at 37 ℃ for 48 hours after adding SNX-2112 with different concentration gradients to Vero cells infected with AdV5 at MOI 1.1 provided in the example of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

1. Illustrative embodiments are explained. This section is an explanatory embodiment expanding on the claims so as to fully understand how the present invention is embodied by those skilled in the art.

The SNX-2112 provided by the embodiment of the invention is used for preparing a medicament and an adenovirus inhibitor for relieving and/or preventing and/or treating adenovirus infection.

The SNX-2112 provided by the embodiment of the invention has the following chemical structural formula:

the adenovirus provided by the embodiment of the invention can be any one or more of

human adenovirus types

1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

The agents provided by the embodiments of the present invention for alleviating and/or preventing and/or treating adenoviral infections act by inhibiting the activity of adenovirus replication.

The medicament for relieving and/or preventing and/or treating adenovirus infection provided by the embodiment of the invention comprises SNX-2112 and a pharmaceutically acceptable carrier.

The dosage form of the medicament for relieving and/or preventing and/or treating the adenovirus infection provided by the embodiment of the invention is any clinically acceptable oral administration dosage form, injection administration dosage form or external administration dosage form.

The medicine for relieving and/or preventing and/or treating adenovirus infection provided by the embodiment of the invention is tablets, capsules, granules, oral liquid and injection.

2. Application examples. In order to prove the creativity and the technical value of the technical scheme of the invention, the part is the application example of the technical scheme of the claims on specific products or related technologies.

The SNX-2112 provided by the embodiment of the invention is applied to the preparation of medicaments and adenovirus inhibitors for relieving and/or preventing and/or treating adenovirus infection. SNX-2112 can effectively inhibit the replication of adenovirus in a non-toxic range, can be further developed into a medicament for treating diseases caused by adenovirus infection, and has wide application prospect. In view of the fact that no drug for the treatment of adenoviral infections is currently approved on the market, the present invention provides a new technology for the treatment of adenoviral infections.

3. Evidence of the relevant effects of the examples. The embodiment of the invention achieves some positive effects in the process of research and development or use, and has great advantages compared with the prior art, and the following contents are described by combining data, diagrams and the like in the test process.

The invention detects the toxicity of SNX-2112 to cells on an African green monkey kidney cell line Vero, and simultaneously determines the inhibition effect of SNX-2112 to two types of adenovirus, namely 3 type adenovirus (AdV 3) and 5 type adenovirus (AdV 5), in the Vero cell line. The results show that the small molecule compound SNX-2112 has significant dose-dependent anti-adenovirus activity against both AdV3 and AdV5. Therefore, the SNX-2112 is a novel antiviral drug for adenovirus, has the advantages of good safety, high selection index, broad-spectrum adenovirus resistance and the like, can be used for developing drugs for treating adenovirus infection, and has wide application prospect.

1. Experimental materials:

(1) Cell line, experimental animal and virus required by experiment

Vero cells were purchased from American Type Culture Collection (ATCC);

the strains used were: adenovirus type B AdV3, adenovirus type C AdV5.

The drugs required for the experiment: SNX-2112 is available from Selleck Chemicals; in cell experiments, drugs were dissolved in DMSO.

Reagents required for the experiment:

DMEM medium, fetal Bovine Serum (FBS) were purchased from GIBCO;

the CellTiter-Glo cell proliferation assay kit was purchased from Promega corporation.

(2) Instrument for experiment

EnSpire multifunctional microplate reader from Perkinelmer;

CO ₂ cell culture chambers were purchased from Thermo corporation;

the Operetta CLS high content imaging analysis system was purchased from PerkinElmer.

2. Experimental methods

2.1 The cytotoxicity of SNX-2112 was measured as follows:

(1) Vero 2X 10 of African green monkey kidney cell line ⁴ Each well was plated in a 96-well plate and cultured for 24 hours.

(2) Adding SNX-2112 diluted with medium to different gradient concentrations, and containing 5% CO at 37 deg.C ₂ The cultivation was continued for 48h.

(3) And (3) detecting the cell viability after the treatment of the drugs with different concentrations so as to detect the cytotoxicity of the SNX-2112.

(4) The median Cytotoxic Concentration (CC) of the drug was calculated by plotting Graphpad against Cell relative Cell viability (Cell viability) versus log drug concentration ₅₀ )。

2.2 evaluation of antiviral activity of SNX-2112 against adenovirus AdV3 in a cell model included:

(1) Vero 2X 10 of African green monkey kidney cell line ⁴ Each well was plated in a 96-well plate and cultured for 24 hours. To test its antiviral efficacy, vero cells were infected with adenovirus AdV3 at 0.55MOI (multiplicity of infection).

(2) Simultaneously adding SNX-2112 diluted with culture medium to different gradient concentrations, and at 37 deg.C, 5% CO ₂ The cultivation was continued for 48h.

(3) The number of virus-infected positive cells (the number of Hexon positive cells) in the wells of the drug-treated and untreated groups was examined by Indirect immunofluorescence assay (IFA) to assess the level of adenovirus AdV3 replication after treatment with different concentrations of SNX-2112.

(4) The half maximal Inhibitory Concentration (IC) of drug to adenovirus AdV3 was calculated by plotting Inhibition rate (Inhibition rate) versus log drug concentration using Graphpad ₅₀ ). The selection index of SNX-2112 on Vero cell line for adenovirus AdV3 was calculated.

2.3 evaluation of the antiviral activity of SNX-2112 against adenovirus AdV5 in a cell model as follows:

1) Vero 2X 10 of African green monkey kidney cell line ⁴ Each well was plated in a 96-well plate and cultured for 24 hours. To test their antiviral effect, vero cells were infected with adenovirus AdV5 at 1.1MOI (multiplicity of infection).

2) Simultaneously adding SNX-2112 diluted with culture medium to different gradient concentrations, and at 37 deg.C, 5% CO ₂ The cultivation was continued for 48h.

3) The number of virus-infected positive cells (Hexon positive cells) in the wells of the drug-treated and untreated groups was examined using an Indirect immunofluorescence assay (IFA) to assess the level of replication of adenovirus AdV5 after various concentrations of SNX-2112 treatment.

4) The half maximal Inhibitory Concentration (IC) of drug to adenovirus AdV5 was calculated by plotting Inhibition rate (Inhibition rate) versus log drug concentration using Graphpad ₅₀ ). The selection index of SNX-2112 for adenovirus AdV5 on Vero cell line was calculated.

2.4 Evaluation of cytotoxicity of SNX-2112 in Vero cell line

(1) Cell culture

After 2 passages, the frozen and recovered cells are subjected to amplification culture by using a DMEM medium containing 10% fetal calf serum and double antibiotics (penicillin 100U/ml and streptomycin 100 mu g/ml), and the inoculation density is not lower than 1x10 ⁴ cell/ml, passage density not higher than 5x10 ⁴ cell/ml。

(2) Drug-treated cells

Vero cells were grown at 1X10 ⁴ Cells/well (volume 100 μ L) were seeded in 96-well cell culture plates and cultured for 24h until the confluency of the wells reached 80%; the drug was prepared in 200. Mu.L of medium (DMEM medium +2% serum + double antibody) per well and added to the corresponding well and mixed well. The drug was set up in 6 concentration gradients with 2 multiple wells at final concentrations of 0.02. Mu.M, 0.06. Mu.M, 0.19. Mu.M, 0.56. Mu.M, 1.67. Mu.M and 5. Mu.M, and 5% CO at 37 ℃ ₂ The cultivation was continued for 48h.

(3) Calculating the toxicity of the drug to the cells in each detection hole

The supernatant was removed and 100. Mu.L of each well was added

Reagents, plates were incubated at room temperature for 10 minutes to stabilize the luminescence signal. Detecting chemiluminescence reading by EnSpire enzyme-linked immunosorbent assay, and measuringAnd calculating the cell survival rate.

Cell viability (%) = drug treated group/untreated control group 100%

The results are shown in FIG. 1, and the SNX-2112 treated Vero cells at the maximum concentration of 5 μ M for 48h has weak difference in cell viability compared with the control group, which indicates that the SNX-2112 has weak toxicity to cells at the concentration, and the half toxicity concentration CC is ₅₀ Greater than 5. Mu.M.

2.5 Evaluation of anti-AdV 3 AdV adenovirus Activity of SNX-2112 in Vero cell line

(1) Cell culture

(2) Drug-treated cells

Vero cells were grown at 1X10 ⁴ Cells/well (volume 100 μ L) were seeded in 96-well cell culture plates and cultured for 24h until the confluency of the wells reached 80%; the infection group was cultured at 37 ℃ for 48 hours in a cell culture incubator with 0.55MOI (multiplicity of infection) of AdV3 virus added thereto, and with drugs added at each concentration gradient (5. Mu.M as an initial concentration, 6 gradients were serially diluted in 3-fold gradient, two wells per gradient) to a total volume of 200. Mu.L of culture medium (DMEM medium +2% serum + double antibody).

(3) Indirect immunofluorescence method for detecting specific fluorescence labeled virus

The cell culture plates were washed twice with the cells in PBS solution and fixed with 4% paraformaldehyde (4% PFA in PBS) for 20 minutes at room temperature. The fixed samples were washed 3 times with PBST (0.05% tween 20 in PBS) and then incubated in blocking buffer (3% BSA,0.3% Triton X-100, and 10% FBS in PBS) for 1 hour at room temperature. Then incubated overnight at 4 ℃ in binding buffer (3% BSA,0.3% Triton X-100 in PBS) with mouse monoclonal antibody against adenovirus hexon protein (dilution 1. After 3 rinses with PBST, the samples were buffered in a conjugate of goat FITC-conjugated anti-mouse secondary antibody (dilution 1 1000) and DAPI (dilution 1Incubate in solution for 1 hour at room temperature in the dark. After rinsing 3 times with PBST, use

CLS ^TM The high content analysis system observes the sample and then takes and analyzes the image.

(4) Calculating the inhibition rate of the drug in each detection hole to the virus

Cells were labeled by DAPI staining, and the intensity of FITC staining represents the level of viral replication. FITC background fluorescence was measured in uninfected control cells. Cells with FITC intensity three times greater than control cells were defined as adenovirus infection positive cells. The ratio of adenovirus infection positive cells in total cells was calculated.

Inhibition (%) =100% - (drug-treated well-blank)/(virus control well-blank) × 100%

As shown in FIG. 2, SNX-2112 significantly inhibited replication of adenovirus AdV3 and was dose dependent with its half effective concentration IC ₅₀ It was 0.17. Mu.M.

(5) Drug selection index calculation

The drug Selection Index (SI) is used for judging the safety range of the drug effect, the selection index is more than 3 to be effective, and the larger the index is, the larger the safety range is. The calculation formula is as follows: SI = CC ₅₀ /IC ₅₀

Combining the data, the selection index of SNX-2112 on Vero for adenovirus AdV3 is more than 10, and the adenovirus AdV3 has effective anti-adenovirus AdV3 activity.

2.6 Evaluation of SNX-2112 Activity against AdV5 adenovirus in Vero cell line

(1) Cell culture

After 2 passages of frozen and recovered cells, performing amplification culture on the cells by using a DMEM culture medium containing 10% fetal calf serum and double antibodies (penicillin 100U/ml and streptomycin 100 mu g/ml), wherein the inoculation density is not lower than 1x10 ⁴ cell/ml, passage density not higher than 5X10 ⁴ cell/ml。

(2) Drug-treated cells

Vero cells were grown at 1X10 ⁴ Cells/well (100. Mu.L volume) were seeded in 96 Kong XiCulturing in a cell culture plate for 24h until the confluence of cell pores reaches 80%; the infection group was cultured at 37 ℃ for 48 hours in a cell culture incubator with addition of 1.1MOI (multiplicity of infection) of AdV5 virus and simultaneous addition of each of the drugs at each concentration gradient (starting at 5. Mu.M, serially diluted at 3-fold gradient for 6 gradients, two multiple wells per gradient) to a total volume of 200. Mu.L of culture medium (DMEM medium +2% serum + double antibody).

The cell culture plates were washed twice with the cells in PBS solution and fixed with 4% paraformaldehyde (4% pfa in PBS) for 20 minutes at room temperature. The fixed samples were washed 3 times with PBST (0.05% tween 20 in PBS) and then incubated in blocking buffer (3% BSA,0.3% Triton X-100, and 10% FBS in PBS) for 1 hour at room temperature. Then incubated overnight at 4 ℃ in binding buffer (3% BSA,0.3% Triton X-100 in PBS) with mouse monoclonal antibody against adenovirus hexon protein (dilution 1. After 3 rinses with PBST, the samples were incubated in a binding buffer of goat FITC-conjugated anti-mouse secondary antibody (dilution 1 1000) and DAPI (dilution 1 10000) for 1 hour at room temperature in the dark. Rinsing with PBST 3 times, and using

Cells were labeled by DAPI staining, and the intensity of FITC staining represents the level of viral replication. FITC background fluorescence was measured in uninfected control cells. Cells with FITC intensity three times higher than the control cells were defined as adenovirus infection positive cells. The ratio of adenovirus infection positive cells in total cells was calculated.

As shown in FIG. 3, SNX-2112 significantly inhibited replication of adenovirus AdV5 in a dose-dependent manner with a half-effective concentration IC ₅₀ It was 0.33. Mu.M.

(5) Drug selection index calculation

The drug Selection Index (SI) is used to determine the safety range of drug effects, with selection indices above 3 being effective, with the larger the index the greater the safety range. The calculation formula is as follows: SI = CC ₅₀ /IC ₅₀

Combining the data, the selection index of SNX-2112 on Vero for adenovirus AdV5 is more than 10, and the active anti-adenovirus AdV5 activity is achieved.

The above description is only for the purpose of illustrating the present invention and the appended claims are not to be construed as limiting the scope of the invention, which is intended to cover all modifications, equivalents and improvements that are within the spirit and scope of the invention as defined by the appended claims.

Claims

1. Use of SNX-2112 in the manufacture of a medicament for the alleviation and/or prevention and/or treatment of adenoviral infection.

2. The use according to claim 1, wherein the adenovirus is one or more of adenovirus type 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.

3. The use of claim 1, wherein the adenovirus comprises a group B adenovirus AdV3 subtype, a group C adenovirus AdV5 subtype.

4. The use according to claim 1, wherein the medicament for ameliorating and/or preventing and/or treating an adenoviral infection comprises SNX-2112 and a pharmaceutically acceptable carrier.

5. The use of claim 1, wherein the adenoviral infection is one or more of a respiratory disease, an intestinal disease, and a corneal disease.

6. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is in any one of clinically acceptable oral administration dosage forms or injection administration dosage forms.

7. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is in any clinically acceptable form for external administration.

8. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating adenovirus infection is a tablet, a capsule, a granule, an oral liquid, an injection.