CN114558022A

CN114558022A - Application of brinell-cidofovir in preparation of anti-pseudorabies virus drugs

Info

Publication number: CN114558022A
Application number: CN202210141948.3A
Authority: CN
Inventors: 王湘如; 呙会会; 国师榜; 刘青芸; 刘慧�; 陈焕春
Original assignee: Huazhong Agricultural University
Current assignee: Huazhong Agricultural University
Priority date: 2022-02-16
Filing date: 2022-02-16
Publication date: 2022-05-31
Anticipated expiration: 2042-02-16
Also published as: CN114558022B

Abstract

The present invention provides an application of brinciclovir in preparing anti-pseudorabies virus medicine, belonging to the field of biological pharmaceutical technology. The present disclosure provides a preparation of a pseudorabies virus resistant drug by brinciclovir, which is capable of inhibiting pseudorabies virus.

Description

Application of brinell-cidofovir in preparation of anti-pseudorabies virus drugs

Technical Field

The disclosure belongs to the technical field of biological pharmacy, and particularly relates to application of brinell-cidofovir in preparation of a medicine for resisting pseudorabies.

Background

Porcine Pseudorabies is a high-contact infectious disease with the symptoms of pig breeding disorder, ataxia, dyspnea and the like caused by Pseudorabies virus (PRV), and is one of the most important viral diseases in the live pig breeding industry. Herds of all ages are susceptible and adult pigs are more recessive. The disease has high mortality and high propagation speed. According to related reports, in 2017, in China, 23 PRV-infected cases diagnosed by mNGS were totally found, 4 of the cases died, and the death rate was 17.4%. 2 vegetative states, 2 ventilators maintained minimal vital signs, 3 coma states, 6 blindness, and 6 lives were self-care only. This indicates that porcine pseudorabies can infect humans, and that the prognosis for most patients after infection is poor, leaving survivors with severe disability and disability.

In the related technology, no specific medicine is available for pseudorabies virus, the pig can be prevented only by the vaccine, once the pseudorabies virus begins to spread in a pig farm, great economic damage can be caused to the pig breeding industry, and meanwhile, the human can be infected. However, the existing vaccine only has a preventive effect on pig infection, and does not have a preventive effect on human beings and the like, so that the development of effective medicaments for the pig infection is urgently and urgently needed.

Disclosure of Invention

The disclosed embodiment provides an application of brinell-cidofovir in preparation of a pseudorabies resisting drug, and the brinell-cidofovir can be used as a drug for treating pseudorabies resisting viruses to treat the pseudorabies resisting viruses.

The technical scheme is as follows:

the embodiment of the disclosure provides application of brinzoledrir in preparation of a pseudorabies virus resisting drug.

In yet another implementation of the present disclosure, the anti-pseudorabies virus drug is for treating at least one of encephalitis, retinitis, or endophthalmitis associated with a pseudorabies virus infection.

In still another embodiment of the present disclosure, there is also provided a pseudorabies virus resistant drug comprising brinciclovir as an active ingredient.

In still another embodiment of the present disclosure, there is also provided a pseudorabies virus resistant drug further comprising a stereoisomer of brinciclovir or a solvate of brinciclovir as an active ingredient.

In yet another implementation of the present disclosure, the medicament further comprises a pharmaceutically acceptable salt of brinciclovir or a solvate of a pharmaceutically acceptable salt of brinciclovir.

In still another embodiment of the present disclosure, the dosage form of the drug is any pharmaceutically acceptable dosage form.

In yet another implementation of the present disclosure, the dosage form of the drug includes at least one of an oral formulation, a spray formulation, and an injection formulation.

In yet another implementation of the disclosure, the medicament is for treating at least one of encephalitis, retinitis, or endophthalmitis associated with a pseudorabies virus infection.

In yet another implementation of the present disclosure, there is also provided a method of using an anti-pseudorabies virus drug prepared with brinciclovir, the method comprising:

administering the anti-pseudorabies virus medicament prepared from brinciclovir to a subject;

the content of the brinell-cidofovir in the anti-pseudorabies virus medicine and the weight ratio of the body weight of the administration object are 10 mg/Kg.

In yet another implementation form of the present disclosure, there is also provided a method of treatment of a human or animal body infected with pseudorabies virus, the method comprising administering the above-described medicament to an infected person infected with pseudorabies virus.

The technical scheme provided by the embodiment of the disclosure has the following beneficial effects:

as the brinell-cidofovir can be applied to treatment of pseudorabies virus resistance, after a human body is infected with the pseudorabies virus, the virus can be inhibited through the brinell-cidofovir, so that related diseases of the pseudorabies virus can be treated.

Drawings

In order to more clearly illustrate the technical solutions in the embodiments of the present disclosure, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present disclosure, and it is obvious for those skilled in the art to obtain other drawings based on the drawings without creative efforts.

FIG. 1 is a diagram of the effect of visualization of anti-PRV of cidofovir of brinell;

FIG. 2 is a schematic representation of the titer of brinciclovir against PRV virus;

FIG. 3 is a schematic representation of the number of copies of cidofovir against PRV virus;

FIG. 4 is a schematic representation of the brinell-cidofovir drug evaluation CC 50;

FIG. 5 is a schematic representation of Bulin cidofovir drug evaluation IC 50;

FIG. 6 is a weight indication for a brinell-cidofovir-treated mouse;

FIG. 7 is the experimental survival curve for mice treated with brinciclovir;

FIG. 8 is a schematic representation of viral load in tissue of a brineespace-treated mouse;

FIG. 9 is a schematic diagram of the treatment of pathological injury in mice by brinciclovir.

Detailed Description

To make the objects, technical solutions and advantages of the present disclosure more apparent, embodiments of the present disclosure will be described in detail with reference to the accompanying drawings.

Alternatively, the structure of brinciclovir is as follows:

the above adopted brinciclovir is provided by the institute of poison medicine of the academy of military medical sciences.

Brin cidofovir (brincidiofovir) is a broad-spectrum antiviral drug with anti-double-stranded dna (dsdna) viral activity, is a nucleotide analogue, is orally active, and is a cidofovir phosphitylated prodrug. Currently, the drug is undergoing phase II/III clinical trials for treatment of patients with severe and conditional DNA virus infections (including cytomegalovirus, adenovirus, herpes simplex virus, vaccinia virus, smallpox or monkeypox virus) and for prophylactic treatment of patients with asymptomatic adenoviremia hematopoietic stem cell transplantation, and has been approved by the U.S. FDA for the use of drugs for treatment of smallpox. Brinciclovir has also promising antiviral therapy in the treatment of PRV (pseudorabies virus) infection in humans.

Optionally, the anti-pseudorabies virus medicament is also for treating at least one of encephalitis, retinitis, or endophthalmitis associated with a pseudorabies virus infection.

Once a human body is infected with the pseudorabies virus, encephalitis, retinitis or endophthalmitis are easy to cause clinically, so the anti-pseudorabies virus medicament can also be used for treating at least one of encephalitis, retinitis or endophthalmitis clinically related to the pseudorabies virus infection of the human body.

In this embodiment, the brinell-cidofovir is also used for treating pseudorabies in other animals, for example, in animals such as cattle, pigs, sheep, dogs, cats, etc.

In another aspect, the embodiments of the present disclosure also provide a pseudorabies virus resistant medicament, which comprises brinzoledrir as an active ingredient.

The medicine can effectively treat the pseudorabies virus.

Optionally, the medicament further comprises a stereoisomer of the brinzoledrvir or a solvate of the brinzoledrvir as an active ingredient.

Optionally, the medicament further comprises a pharmaceutically acceptable salt of brinzoledrvir or a solvate of a pharmaceutically acceptable salt of brinzoledrvir.

The drug comprises the above substances, and can be rapidly absorbed by a subject when the drug is applied to the subject, so that the spreading of the pseudorabies virus can be effectively inhibited.

Optionally, the dosage form of the drug is any pharmaceutically acceptable dosage form.

The medicine is used as a plurality of dosage forms, so that the application range of the medicine can be enlarged, the medicine can enter a dosing object in different forms, and the medicine is convenient to take.

For example, the pharmaceutical dosage form includes at least one of oral preparation, spray preparation, and injection preparation.

Optionally, the medicament is for treating one of encephalitis, retinitis, or endophthalmitis associated with a pseudorabies virus infection.

The embodiment of the disclosure also provides a using method of the anti-pseudorabies virus medicament prepared from the brinciclovir, and the using method comprises the following steps:

administering an anti-pseudorabies virus drug prepared from brinciclovir to a subject, wherein the weight ratio of the content of the brinciclovir in the anti-pseudorabies virus drug to the body weight of the subject is 10 mg/Kg.

When the brinell-cidofovir is applied to an administration object according to the proportion, the growth of pseudorabies virus can be effectively inhibited, and then the pseudorabies can be effectively treated.

In yet another aspect, the disclosed embodiments also provide a method of treatment of a human or animal body infected with pseudorabies virus, the method comprising administering the above medicament to an infected person infected with pseudorabies virus.

In addition, in order to clearly illustrate the application of the brinciclovir provided in the examples of the disclosure in the preparation of anti-pseudorabies virus drugs, the following experimental contents are further illustrated.

Then, the related nouns are explained first.

The median tissue infection (TCID50) is the highest viral dilution that causes 50% of the animals or cells to die or become diseased after the virus infects them.

Viral titer is the virulence, or titer, of the virus. Units measuring viral titer are Minimal Lethal Dose (MLD), Minimal Infectious Dose (MID), and median lethal dose (LD50), with LD50 being the most commonly used. By median lethal amount is meant the amount of virus that will kill half of the test animals over a given period of time.

Cytotoxicity (cytoxic) is a simple cell killing event caused by cells or chemicals, independent of the cell death mechanism of apoptosis or necrosis.

In a first aspect, brinell-cidofovir is screened as an anti-pseudorabies virus (PRV) drug.

Firstly, a PRV antiviral drug high-throughput screening model is constructed to screen the brinell-cidofovir which has a good PRV inhibition effect.

Wherein the screening conditions are as follows: monolayer PK-15 cells were prepared from 96-well cell plates, virus 0.01MOI, drug concentration 10. mu.M, and cultured for 36 h. The multifunctional microplate reader measures the fluorescence value and calculates the inhibition rate.

The larger the inhibition rate is, the stronger the PRV resistance of the drug to be screened is, the inhibition rate of the control group and the experimental group is compared, and the inhibition effect of the screened drug on the PRV is determined. The brinell-cidofovir with good PRV proliferation inhibition effect is screened from a large amount of medicines.

Then, the action of the brinell-fovir infects the cells with PRV strain (wherein the strain is provided with a fluorescent label in advance), the infected cells are 0.01MOI (multiplicity of infection, ratio of virus to cell number in infection), the concentration of the brinell-fovir is 10 mu M, and after culturing for 36h, pictures are taken by a fluorescent microscope.

The PRV strain is the strain hSD-1/2019 of pseudorabies virus, and is provided by university of agriculture in Huazhong. The PRV strain is attached with a fluorescent label, and when the cells are infected with the PRV strain, it can be confirmed by fluorescence. The cells were PK-15 cells.

In this example, the cell growth medium used consisted of: 89% DMEM medium, 10% fetal bovine serum and 1% double antibody were prepared in a sterile environment and stored in a refrigerator at 4 ℃.

The adopted cell maintenance culture solution comprises the following components: 96% DMEM medium, 3% fetal bovine serum and 1% diabase, after preparation, were filter sterilized and stored in a 4 ℃ refrigerator.

The above PRV dilutions were diluted with cell maintenance medium according to the half tissue infection amount (TCID50) of the virus stock and the experimental specifications.

The inhibition effect of the brinciclovir on PRV is visually confirmed by taking a picture through a fluorescence microscope.

FIG. 1 is a graph showing the effect of cidofovir, which is a brin, on PRV, and in combination with FIG. 1, the left graph in FIG. 1 shows that the fluorescence labeling of PK-15 cells is greatly reduced when the above cidofovir, which is a brin, acts on PK-15 cells after PRV infection. The middle panel in FIG. 1 is PK-15 cells after PRV infection (blank, without added brin cidofovir), from which it can be seen that fluorescence labeling also increased greatly when PK-15 cells proliferated, indicating that the number of viruses was also increasing. The right panel in FIG. 1 shows that PK-15 cells were not infected with PRV and were simultaneously supplemented with brinzolpidevir, and from this figure, it can be seen that no fluorescence appeared when PK-15 cells proliferated. Therefore, the valaciclovir hydrochloride can better inhibit the increment of the PRV strain hSD-1/2019 virus. In contrast, in the two experimental groups compared, no fluorescence was observed.

Then, the amount of infection of half of the tissues after the effect of cidofovir against PRV strain was determined (TCID 50).

The berbamine cidofovir acts on a PRV strain, the virus is 0.01MOI, the using concentration of the medicine is 10 mu M, the PRV strain is cultured for 36h and then put into a refrigerator at minus 80 ℃ for freeze thawing for 3 times, and virus liquid is collected. Adding 100 mu L of cell suspension into each hole of a 96-hole micro-culture plate to ensure that the cell amount reaches 2-3 multiplied by 10⁵One per mL. According to the estimated poison price, PRV strain hSD-1/2019 is continuously diluted by 10 times in a virus tube by maintenance fluid, and the dilution ratio is 10 times^-5～10^-8A column of 8 wells, 100. mu.L per well, was inoculated for each dilution. Two longitudinal rows of normal cell controls (100. mu.L maintenance plus 100. mu.L cell suspension) were set; the results were observed and recorded day by day (after 5-7 days), and the TCID50 was calculated using the Karber method.

Referring to FIG. 2, the abscissa of FIG. 2 represents the number of viruses infecting cells before and after the action of brinciclovir on PK-15 cells. The black bars represent the number of cells infected with virus before the effect of brinciclovir on PK-15 cells, and the grey bars represent the number of cells infected with virus after the effect of brinciclovir on PK-15 cells. The ordinate is the viral titerExpressed in lg (TCID 50/0.1). According to comparison, PRV (PRV) virus titer of the drug group for the brin cidofovir is 10^6.12Down to 10^1.85Can show that the brin cidofovir has better inhibition effect on the increment of PRV strain hSD-1/2019

Next, the number of viral copies of cidofovir after exposure to PRV strain hSD-1/2019 was determined.

PK-15 cells are inoculated in a six-hole cell culture plate, and a cell growth culture solution is added until the cells grow to 70-80 percent for use.

The grouping mode comprises a brin cidofovir medication group, a virus control group and a blank control group. Inoculating virus solution with infection multiplicity of 0.01MOI into six-well cell culture plate, adsorbing at 37 deg.C for 1h, removing virus diluent, washing with PBS for 2-3 times, and culturing at 37 deg.C in 5% CO2 for 36 h. And taking the cell culture plate out of the incubator, washing the cell culture plate for 3 times by PBS (phosphate buffer solution), freezing and thawing the cell culture plate for 3 times in a refrigerator at minus 80 ℃, collecting virus liquid to extract DNA, detecting the Ct value of each sample by using a TaqMan probe fluorescence quantitative method, and calculating the virus copy number.

The probe (probe 5 'has a fluorescent group and 3' has a fluorescence quenching group) used in FQ-PCR in the examples of the present invention is shown in Table 1.

TABLE 1 FQ-PCR primer and Probe sequences used

FIG. 3 is a graph showing the copy number of cidofovir in brining against PRV virus, and in combination with FIG. 3, the abscissa in FIG. 3 represents the number of infecting viruses of cells before and after the action of cidofovir in brining on PK-15 cells, respectively. The left histogram represents the cell number of virus-infected PK-15 cells, and the right histogram represents the cell number of virus-infected PK-15 cells after exposure to the cidofovir, brin. The ordinate is the viral copy number. The result shows that the brineefovir has good PRV proliferation inhibiting activity, and the copy number of the viral genome is reduced by more than 250 times.

In a second aspect, the antiviral effect of brinzoledrir on pseudorabies virus in vitro.

First, the CCK-8 method was used to perform CC50 determination of Bulin cidofovir cytotoxicity against PK-15. The cell maintenance solution containing 3% FBS is used as a solvent, and the brinell cidofovir is diluted to obtain brinell cidofovir dilution solutions with 5 concentrations of 5 MuM, 10 MuM, 20 MuM, 40 MuM and 80 MuM.

After the PK-15 cells grew to 70-80%, cell wells were added at different concentrations and 3 replicate wells were set for each group.

After 36h, 10% CCK-8 is added, and after 1h of action, the absorbance value is detected at 450 nm. The inhibition was calculated from the measured absorbance values.

Inhibition rate ═ [ (experimental well-blank)/(control well-blank) ] × 100%.

Drug CC50 values were calculated using nonlinear regression analysis of the graghpag 8.0 software. The calculation gave a CC50 value of 22.32 μ M for brinciclovir, indicating that 10 μ M brinciclovir used in this experiment is a safe dose and is less toxic to PK-15 cells (see figure 4).

While the abscissa of fig. 4 represents the concentration of cidofovir, and the ordinate represents the cell activity, it can be seen in fig. 4 that the cell activity gradually decreases as the concentration of the drug increases. Combining the above calculations for a CC50 value of 22.32. mu.M for brinciclovir, it is known that 10. mu.M less than 22.32. mu.M is a safe dose.

Next, the median inhibitory concentration of budesonide for PRV was determined (IC 50).

The cell maintenance solution containing 3% FBS is used as a solvent, and the brinell-cidofovir is diluted to obtain brinell-cidofovir dilution solutions with concentrations of 0.16 mu M, 0.32 mu M, 0.63 mu M, 1.25 mu M and 2.5 mu M which are 5 concentrations in total.

When the PK-15 cells grow to 70-80%, adding cell wells according to different concentrations, setting 3 repeated wells in each group, and simultaneously adding a PRV strain with the virus titer of 0.01 MOI. Waiting for 4h after the cells are completely diseased, adding 10% CCK-8, and detecting the absorbance value at 450nm after acting for 1 h.

The inhibition was calculated from the measured absorbance values. Inhibition rate ═ [ (experimental well-blank)/(control well-blank) ] × 100%. Drug IC50 values were calculated using nonlinear regression analysis of the graghpag 8.0 software.

The IC50 value for brinciclovir was calculated to be 0.5739. mu.M (see FIG. 5). In fig. 5, the abscissa represents the concentration of budesonide, and the ordinate represents the inhibition rate of PRV, and when the inhibition rate of the ordinate is 50%, it can be seen that the concentration of budesonide is much less than 1 μ M, i.e. the lower concentration of budesonide can inhibit PRV proliferation well.

In the embodiment, the brinell-cidofovir is also evaluated through the drug selection index SI, and the drug selection index can evaluate whether the inhibition effect of the brinell-cidofovir on the PRV is safe or not.

The drug selection index SI, which is CC50/IC50, can be calculated by a calculation formula.

The drug selection index of the brinciclovir is 41.0370, and a higher drug selection index indicates that the drug is safer. Namely, the preparation of the anti-pseudorabies virus medicament by the brin cidofovir is very safe.

In a third aspect, the antiviral effect of brinzoledrir on pseudorabies virus in vivo.

First, a PRV strain is amplified.

The amplification method is as follows: culturing PK-15 cells, when 80-90% of the cell monolayer is fully paved, washing the cells by DMEM, inoculating PRV strain hSD-1/2019 with 0.1MOI titer, incubating at 37 ℃ for 1h, discarding virus solution, adding cell culture solution containing 2% FBS, incubating at 37 ℃ and 5% CO₂Culturing, when cytopathic effect reaches 80-90%, collecting cells, repeatedly freezing and thawing at-80 deg.C for 3 times, 4 deg.C, 8000rpm, centrifuging for 5min, collecting supernatant, and freezing and storing at-80 deg.C.

Subsequently, the virus titer of the amplified PRV strain was determined.

The method comprises the following steps: the PK-15 is paved in a 96-well plate, when the cell fusion degree reaches 80-90%, DMEM is used for washing cells, and PRV is diluted by 10 times (10 times)^-1-10^-9) Cells were inoculated, 100. mu.L/well, 3 wells repeated for each dilution. Culturing at 37 deg.C with 5% CO2 for 5-7d, observing cytopathic effect (CPE) every day, recording cytopathic effect, and applying ReeThe d-Muench statistic calculates the TCID50 of the virus.

The challenge dose was then determined by determining the median lethal dose (LD50) of PRV strain hSD-1/2019 to mice.

For example, 40 Balb/C mice were randomly divided into 5 groups of 8 mice each, and each group was injected with 10 mice each⁴TCID50、10³TCID50、10²TCID50、10¹PRV strains hSD-1/2019 for TCID50 and 0TCID 50.

The death of each group of mice was recorded daily and two weeks later, LD50 of PRV strain hSD-1/2019 was 101.88 and 6.5LD50 was used as the challenge.

The antiviral effect of the brinell-cidofovir on the pseudorabies virus in vivo is researched through a mouse challenge protection experiment.

In the experiment, Balb/C mice are used as research objects, PRV strains hSD-1/2019 of infected people are separated, and an animal model is established by the infected mice for carrying out a virus attack protection experiment.

20 Balb/C mice (weight 17g +/-2 g, female) aged 6 weeks were randomly divided into 4 groups, namely a brin cidofovir treatment group, an acyclovir treatment group, a virus control group and a blank control group. Except for the blank group of mice, each group of mice was treated by injection with 0.1mL of 500TCID50 PRV.

The treatment is carried out for 5 days by using the dose of 10mg/Kg/d of the brinciclovir and the acyclovir. The blank group was given the same volume of physiological saline. The time to death, mortality, clinical symptoms, viral load and histopathological lesions were recorded during the experiment. Mortality and clinical symptoms results indicated that the mice in the blank group were all normal with no clinical symptoms and death.

Fig. 6 is an indication of the weight of mice treated with brinciclovir, see fig. 6, wherein the abscissa represents the number of days of viral infection and the ordinate represents the weight of the mice corresponding to each group, and in combination with fig. 6, it can be seen that the mice in the virus control group begin to develop pruritus symptoms at day 3 after the challenge, and die in succession, and die in total at day 7 (see curve b in fig. 7). Clinical symptoms appeared on day 6 and all died on day 8 in the acyclovir treated group. The mice in the brinell-cidofovir-treated group developed mild itching symptoms in the 5 th part, and disappeared symptoms on the 7 th day, and by the end of the 14-day experimental period, all mice in the brinell-cidofovir-treated group survived (see curve a in fig. 7).

Then, the viral load was measured in the mouse tissue organ. Mice in each group were sacrificed when they were dying, brains and lungs of tissues with higher viral load were collected, and viral load in the tissues and organs was examined.

The test results based on absolute fluorescence quantification show that the viral load in the brinciclovir-treated group is significantly lower than that of the virus control group. The virus load of the acyclovir treatment group is not obviously different from that of the virus control group; wherein no viral load was detected in the tissues of the placebo group.

Fig. 8 is a schematic diagram of the viral load of the tissue of the mice treated by the brinciclovir, and referring to fig. 8, the ordinate in fig. 8 is the virus copy number, the left histogram is the viral load of the brain tissue in the mice of the virus control group, and the viral load of the lung tissue in the mice of the virus control group of the right histogram is larger than the viral load of the brain tissue.

Pathological section experiments were performed on mouse tissues.

After the mouse was dissected, the affected part of the organ was removed with scissors. Fixing the tissue blocks in 4% formaldehyde for more than 24 h; the fixed organs were trimmed to small pieces with a razor blade having a clean cut of about 6mm × 6mm × 1mm, and the small pieces were placed in new 4% formaldehyde and fixed again. Sequentially carrying out the steps of flushing, dehydrating, transparentizing, waxing, embedding, slicing, unfolding, sticking, baking and the like; finally HE staining, mounting and observation of the sections using an optical microscope were performed and photographed.

Fig. 9 is a schematic diagram of pathological lesions of mice treated with brinciclovir, see fig. 9, wherein the left side in fig. 9 is pathological lesions of mice in the virus control group, the middle is pathological lesions of mice in the brinciclovir treatment group, and the right side is pathological lesions of mice in the acyclovir treatment group. The results show that the tissue integrity of the lung and brain of the mice in the brinciclovir-treated group is better than that of the non-administered group.

The experiments show that the cidofovir, brin, can inhibit the proliferation of PRV strain hSD-1/2019 infecting human in Balb/C mice.

The above description is intended to be exemplary only and not to limit the present disclosure, and any modification, equivalent replacement, or improvement made without departing from the spirit and scope of the present disclosure is to be considered as the same as the present disclosure.

Claims

1. An application of brin cidofovir in preparing the medicine for treating pseudorabies is disclosed.

2. The use of claim 1, wherein the anti-pseudorabies virus medicament is for the treatment of at least one of encephalitis, retinitis, or endophthalmitis associated with pseudorabies virus infection.

3. A pseudorabies virus-resistant medicament comprising brinzoledrir as an active ingredient.

4. The drug according to claim 3, further comprising a stereoisomer of brinciclovir or a solvate of brinciclovir as an active ingredient.

5. The medicament of claim 3, further comprising a pharmaceutically acceptable salt of brinciclovir or a solvate of a pharmaceutically acceptable salt of brinciclovir.

6. The medicament of claim 4, wherein the medicament is in any pharmaceutically acceptable dosage form.

7. The medicament of claim 4, wherein the dosage form of the medicament comprises at least one of an oral preparation, a spray preparation and an injection preparation.

8. The medicament of claim 4, wherein the medicament is for treating at least one of encephalitis, retinitis, or endophthalmitis associated with pseudorabies virus infection.

9. A method of using an anti-pseudorabies virus medicament prepared from brinciclovir, the method comprising:

the content of the brinciclovir in the anti-pseudorabies virus medicine and the body weight ratio of the drug administration object are 10 mg/Kg.

10. A method of treatment of the human or animal body for infection by pseudorabies virus, the method comprising administering a medicament as claimed in any one of claims 3 to 8 to an infected person infected with pseudorabies virus.