CN114652728A - Application of Apitolisib in preparation of medicine for resisting adenovirus infection - Google Patents
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Abstract
The invention belongs to the technical field of biomedicine, and discloses application of Apitolisib 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. The medicament for alleviating and/or preventing and/or treating the adenovirus infection comprises Apitolisib and a pharmaceutically acceptable carrier. The invention provides application of a small molecular compound Apitolisib in preparation of a medicament for treating adenovirus infection, and provides a safe and effective small molecular compound for clinical treatment of adenovirus. Apitolisib can effectively inhibit 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 prospects.
Description
Technical Field
The invention belongs to the technical field of biomedicine, and particularly relates to application of Apitolisib 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 proteins VII and protamine-like proteins 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 a very important role in the process of virus infection of cells. 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 present in the capsid is a small amount of capsid protein IVa2 involved in genome packaging and adenovirus protease (AVP) formation.
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 1 type, 3 type, 4 type, 5 type, 7 type, 11 type, 14 type, 40 type, 41 type and 55 type, wherein adenovirus flow behaviors of 3 type and 5 type are dominant. It was found that various types of adenoviruses have highly conserved genomes except for the hexon, fiber, and penton genes, 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 E-type adenovirus infection, and often appear in the form of pharyngeal conjunctivitis or Epidemic Keratoconjunctivitis (EKC) in the recruited recruits. B. Adenovirus type D or E also frequently causes acute respiratory diseases 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, where infected newborns, children and immunocompromised populations (hematopoietic stem cells and organ transplant patients) can often cause more serious illness and even death.
Currently, there are no approved antiviral drugs for the treatment of adenoviral infections. Certain DNA/RNA synthesis-inhibiting antiviral drugs (e.g., cidofovir, ganciclovir, and ribavirin) approved for the treatment of other viral infections 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 effects. Therefore, there is a need to develop other safer and more effective anti-adenoviral agents.
Apitolisib (GDC-0980RG7422, GNE 390) is a potential novel therapeutic agent for treating lymphoma, solid tumor and breast cancer, is a novel and effective mTOR inhibitor, and can inhibit the proliferation of various human tumor cell lines. Apitolisib inhibits the migration and invasion of tumor cells and epithelial-mesenchymal transition by inhibiting PI3K/Akt/mTOR signal pathways abnormally activated by the tumor cells, and simultaneously participates in regulating angiogenesis and immunoreaction in a Tumor Microenvironment (TME), so that the tumor is regressed. However, no report on the treatment of adenovirus infection by Apitolisib has been found.
Through the above analysis, the problems and defects of the prior art are as follows:
(1) there are no reports of Apitolisib for treatment of adenoviral infections.
(2) The prior art relates to a medicament for treating adenovirus infection, which has low drug effect and poor effect.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides the application of Apitolisib in preparing a medicament for resisting adenovirus infection.
The invention is realized in such a way that Apitolisib is used for preparing a medicament for alleviating and/or preventing and/or treating adenovirus infection.
Further, the Apitolisib structural formula 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 adenovirus infection acts by inhibiting the activity of adenovirus replication.
Further, the medicament for alleviating and/or preventing and/or treating the adenovirus infection comprises Apitolisib 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.
Another purpose of the invention is to provide an application of Apitolisib in preparing adenovirus inhibitors.
In combination with the technical solutions and the technical problems to be solved, please analyze the advantages and positive effects of the technical solutions to be protected in the present invention from the following aspects:
first, aiming at the technical problems existing in the prior art and the difficulty in solving the problems, the technical problems to be solved by the technical scheme of the present invention are closely combined with the technical scheme to be protected and the results and data in the research and development process, and some creative technical effects brought after the problems are solved are analyzed in detail and deeply. The specific description is as follows:
aiming at the current situation that the prior art has no antiviral drug infected by the adenovirus, the invention provides a novel anti-adenovirus drug-Apitolisib by combining the experimental data of low cytotoxicity of Apitolisib in Vero cells, high antiviral activity of Apitolisib on two adenoviruses and the like in the research and development process, provides a new technology of the antiviral drug infected by the adenovirus, and provides a brand new therapy and more treatment options for treating diseases caused by the adenovirus infection.
The invention provides application of a small molecular compound Apitolisib in preparation of a medicament for treating adenovirus infection, and provides a safe and effective small molecular compound for clinical treatment of adenovirus. Apitolisib can effectively inhibit 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 prospects.
Apitolisib of the invention is a small molecule compound that is specific for the CC of Vero cells50(half lethal concentration) was 3.00. mu.M. Apitolisib is able to dose-dependently inhibit viral replication for both adenoviruses (AdV3 and AdV 5). IC of AdV3 in Vero cells50(median inhibitory concentration) 0.08 μ M only, IC for AdV550It was 0.27. mu.M. By calculation, the Selection Index (SI) of Apitolisib was 36.44 and 10.96 on AdV3 and AdV5, respectively, indicating that Apitolisib has broad-spectrum activity against adenoviral replication.
Secondly, considering the technical scheme as a whole or from the perspective of products, the technical effect and advantages of the technical scheme to be protected by the invention are specifically described as follows:
the invention provides a novel anti-adenovirus medicament-Apitolisib, which makes up the technical defect that the prior art has no anti-virus medicament aiming at adenovirus infection.
The Apitolisib serving as a novel antitumor drug in research and development successfully passes phase I clinical experiments, and is in phase II clinical experiments at present. Indicating that the medicine has good safety. If the indications are expanded to the medicines for treating the adenovirus infection, the medicine taking period is shorter, and the expected safety is better.
Third, as inventive supplementary proof of the claims of the present invention, there are several important aspects as follows:
(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 and Apitolisib containing 5% CO at 37 ℃ with different concentration gradients provided in the examples of the present invention2After incubation in the incubator of (1) for 48 hours, a cell viability profile of the Vero cells relative to the non-drug treated cells was determined;
FIG. 2 is a graph showing the percentage of inhibition of AdV3 of Vero cells after incubation at 37 ℃ for 48 hours with AdV3 infected with Apitolisib with different concentration gradients added to Vero cells according to the present invention, at an MOI of 0.55, versus untreated drug cells after virus infection;
FIG. 3 is a graph showing the percentage of inhibition of AdV5 of Vero cells treated with different drug concentration gradients to non-drug-added cells after incubation at 37 ℃ for 48 hours with AdV5 infected with MOI 1.1 after adding Apitolisib with different concentration gradients to Vero cells 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.
First, an embodiment is 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 Apitolisib 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 Apitolisib chemical structural formula provided by the embodiment of the invention is as follows:
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 medicine for alleviating and/or preventing and/or treating the adenovirus infection provided by the embodiment of the invention comprises Apitolisb 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.
And II, application embodiment. 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 Apitolisib 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. Apitolisib 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 adenovirus infection is currently approved on the market, the present invention provides a new technology for the treatment of adenovirus infection.
And thirdly, evidence of relevant effects of the embodiment. 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 Apitolisib to cells on a Vero cell line of African green monkey, and simultaneously determines the inhibition effect of Apitolisib to two types of adenovirus, namely 3 type adenovirus (AdV3) and 5 type adenovirus (AdV5) in the Vero cell line. The results show that the small molecule compound Apitolisib has significant dose-dependent anti-adenoviral activity against both AdV3 and AdV 5. Therefore, the Apitolisib 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 prospects.
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 AdV 5.
The drugs required for the experiment: apitolisib 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;
CO2cell culture chambers were purchased from Thermo corporation;
the Operetta CLS high content imaging analysis system was purchased from PerkinElmer.
2. Experimental methods
2.1 cytotoxicity assays of Apitolisib are as follows:
(1) vero 2X 10 of African green monkey kidney cell line4Each well was plated in a 96-well plate and cultured for 24 hours.
(2) Adding Apitolisib diluted with culture medium to different gradient concentrations, 5% CO at 37 deg.C2The cultivation was continued for 48 h.
(3) And (3) detecting the cell viability after the treatment of the medicines with different concentrations so as to detect the cell toxicity of the Apitolisib.
(4) The median Cytotoxic Concentration (CC) of the drug was calculated by plotting Graphpad against Cell relative Cell viability (Cell viability) versus log drug concentration50)。
2.2 evaluation of antiviral activity of Apitolisib on adenovirus AdV3 in cell models included:
(1) vero 2X 10 of African green monkey kidney cell line4Each well was plated in a 96-well plate and cultured for 24 hours. To test their antiviral efficacy, Vero cells were infected with adenovirus AdV3 at 0.55MOI (multiplicity of infection).
(2) At the same time, Apitolisib diluted with medium to different gradient concentrations and containing 5% CO at 37 deg.C was added2The cultivation was continued for 48 h.
(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 AdV3 after treatment with varying concentrations of Apitolisib.
(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 Graphpad50). The selection index of Apitolisib on Vero cell line for adenovirus AdV3 was calculated.
2.3 evaluation of the antiviral activity of Apitolisib on adenovirus AdV5 in a cell model as follows:
1) vero 2X 10 of African green monkey kidney cell line4Each well was plated in a 96-well plate and incubated for 24 h. To test their antiviral effect, Vero cells were infected with adenovirus AdV5 at 1.1MOI (multiplicity of infection).
2) At the same time, Apitolisib diluted with medium to different gradient concentrations and containing 5% CO at 37 deg.C was added2The cultivation was continued for 48 h.
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 treatment with varying concentrations of Apitolisib.
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 Graphpad50). The selection index of Apitolisib on Vero cell line for adenovirus AdV5 was calculated.
2.4 evaluation of the cytotoxicity of Apitolisib in Vero cell lines
(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 1x104cell/ml, passage density not higher than 5x104 cell/ml。
(2) Drug-treated cells
Vero cells were grown at 1X104Cells/well (volume 100 μ L) were seeded in 96-well cell culture plates and cultured for 24h until the cell well confluence reached 80%; the drugs were prepared in 200. mu.L of medium (DMEM medium + 2% serum + double antibody) per well and added to the corresponding wells and mixed well. The drug was set up in 8 concentration gradients with 2 multiple wells at each gradient concentration to final concentrations of 0.002. mu.M, 0.007. mu.M, 0.02. mu.M, 0.06. mu.M, 0.19. mu.M, 0.56. mu.M, 1.67. mu.M and 5. mu.M with 5% CO at 37 ℃2The cultivation was continued for 48 h.
(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. The chemiluminescence readings were detected with an ensspire microplate reader and the cell viability was calculated.
Cell survival (%). percent vs. drug treated/untreated control 100%
As shown in FIG. 1, the cell viability of Vero cells treated with Apitolisib at the maximum concentration of 5 μ M for 48h was slightly different from that of the control group, indicating that Apitolisib is slightly toxic to cells at this concentration and half toxic concentration CC is present50At 3.00. mu.M.
2.5 evaluation of the Activity of Apitolisib against AdV3 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 1x104cell/ml, passage density not higher than 5X104 cell/ml。
(2) Drug-treated cells
Vero cells were grown at 1X104Cells/well (volume 100 μ L) were seeded in 96-well cell culture plates and cultured for 24h until the cell well confluence reached 80%; the infection group was cultured at 37 ℃ for 48 hours in a cell culture incubator at 0.55MOI (multiplicity of infection) with the addition of AdV3 virus at each concentration gradient (starting at 5. mu.M, 8 gradients 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 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 in blocking buffer (3% BSA, 0.3% Triton X-100, and 10% FBS in PBS)Incubate for 1 hour at room temperature. The cells were 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: 200). After 3 washes 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
CLSTMThe 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 higher than the 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, Apitolisib significantly inhibited replication of adenovirus AdV3 in a dose-dependent manner with a half-effective concentration IC50It was 0.08. 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 ═ CC50/IC50
In combination with the above data, Apitolisib has a selection index of 36.44 for adenovirus AdV3 on Vero, and has effective anti-adenovirus AdV3 activity.
2.6 evaluation of the Activity of Apitolisb against AdV5 adenovirus in Vero cell line
(1) Cell culture
After 2 passages, the frozen and recovered cells were used with 10% fetal calf serum and double antibody (penicillin)100U/ml, streptomycin 100 mug/ml) DMEM medium amplification culture, the inoculation density is not lower than 1x104cell/ml, passage density not higher than 5x104 cell/ml。
(2) Drug-treated cells
Vero cells were grown at 1X104Cells/well (volume 100 μ L) were seeded in 96-well cell culture plates and cultured for 24h until the cell well confluence reached 80%; the infection group was cultured at 37 ℃ for 48 hours in a cell culture incubator at 1.1MOI (multiplicity of infection) of AdV5 virus, and simultaneously with each of the drugs at each concentration gradient (starting at 5. mu.M, 8 gradients serially diluted at 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 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. The cells were 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: 200). After 3 washes 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
CLSTMThe 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 a result, as shown in FIG. 3, Apitolisib significantly inhibited replication of adenovirus AdV5 in a dose-dependent manner with a half-effective concentration IC50It was 0.27. 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 ═ CC50/IC50
Combining the data, the selection index of Apitiolisib on Vero for adenovirus AdV5 is 10.96, and the Apitiolisib has effective anti-adenovirus AdV5 activity.
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 (10)
1. Use of Apitolisib for the preparation of a medicament for the alleviation and/or prevention and/or treatment of adenoviral infections.
2. The use according to claim 1, wherein the adenovirus is one of adenovirus type 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.
3. The use according to claim 1, wherein the adenovirus is a plurality of adenovirus types 1, 3, 4, 5, 7, 11, 14, 40, 41 and 55.
4. The use of claim 1, wherein the adenovirus comprises group B adenovirus AdV3 subtype.
5. The use according to claim 1, wherein the adenovirus comprises group C adenovirus AdV5 subtype.
6. The use according to claim 1, wherein the medicament for alleviating and/or preventing and/or treating an adenoviral infection comprises Apitolisib and a pharmaceutically acceptable carrier.
7. The use according to claim 1, wherein the pharmaceutical formulation for alleviating and/or preventing and/or treating adenoviral infection is any one of clinically acceptable oral dosage forms.
8. 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 parenteral administration.
9. 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.
10. 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.
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| US20140206678A1 (en) * | 2011-01-27 | 2014-07-24 | Kadmon Corporation, Llc | Inhibitors of mtor kinase as anti -viral agent |
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