Use of nm107 in combating infectious pancreatic necrosis virus

Abstract

The application discloses application of NM107 in resisting infectious pancreatic necrosis virus. The application provides application of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or the derivative thereof or the pharmaceutically acceptable salt thereof as an active ingredient in preparation of a product for resisting infectious pancreatic necrosis virus. NM107 has an anti-IPNV effect in vivo and in vitro, and is a potential candidate drug for resisting IPNV infection.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of aquaculture, in particular to the application of NM107 in the resistance to infectious pancreatic necrosis virus. BACKGROUND

[0002] Infectious pancreatic necrosis (IPN) is a disease that has attracted much attention in aquaculture, mainly infecting salmonids such as rainbow trout (Oncorhynchus mykiss) and Atlantic salmon (Salmo salar), with a mortality rate of 80-90%. The Ministry of Agriculture and Rural Affairs lists it as a category III animal epidemic. Its pathogen, infectious pancreatic necrosis virus (IPNV), is a waterborne double-stranded RNA virus belonging to the Birnaviridae family, and is considered to be the most common pathogen in aquatic animals, distributed worldwide. IPNV is an unenveloped icosahedral virus with an average size of about 60-65 nm, and its genome consists of two segments of dsRNA named A and B. Fragment A contains two open reading frames (ORF), which encode a polyprotein composed of VP2, VP4 and VP3, and a non-structural protein VP5. Segment B encodes RNA-dependent RNA polymerase (RdRp) VP1, which is essential for viral RNA replication, and is therefore considered an important target for the development of antiviral drugs.

[0003] 2'-C-methylcytidine (NM107) is a member of the 2'-C-methyl ribonucleoside class of compounds. This class of substances has been previously shown to inhibit RdRp. Studies have shown that the 3'-pentyl ester prodrug of NM107, NM283, has antiviral effects on the RNA virus hepatitis C virus (HCV), and NM107 has effective anti-DENV activity in a dengue virus (DENV) subgenomic RNA replicon and infection system. NM107 can inhibit the replication of mouse norovirus (MNV) in vitro and reduce the replication of norovirus in a dose-dependent manner. However, the relationship between NM107 and waterborne birnavirus is not clear. SUMMARY

[0004] The purpose of the present application is to provide the application of NM107 in the resistance to infectious pancreatic necrosis virus. NM107 is 2'-C-methylcytidine.

[0005] In the first aspect, the present application claims the application of NM107 or its derivative or its pharmaceutically acceptable salt or a substance with NM107 or its derivative or its pharmaceutically acceptable salt as an active ingredient in the preparation of a product for resisting infectious pancreatic necrosis virus.

[0006] The anti-IPNV can specifically inhibit IPNV before, during and after IPNV infection.

[0007] In a second aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for preventing and / or treating a disease caused by IPNV infection.

[0008] The disease can be specifically IPND.

[0009] In a third aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for inhibiting IPNV RNA replication.

[0010] In a fourth aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for reducing IPNV RNA expression at the level of fish cells.

[0011] In a fifth aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for reducing IPNV RNA expression at the level of fish.

[0012] In a sixth aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for reducing IPNV titer at the level of fish cells.

[0013] In a seventh aspect, the present application claims protection for the use of NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof or a substance taking NM107 or a derivative thereof or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for reducing IPNV titer at the level of fish.

[0014] In the fourth and sixth aspects above, the fish cells can be Chinook salmon embryo cells (such as CHSE-214 cells).

[0015] In the fifth and seventh aspects above, the fish can be a fish capable of being infected by IPNV.

[0016] Further, the fish body can be rainbow trout.

[0017] In the above aspects, the NM107 is a compound shown in Formula I;

[0018]

[0019] Formula I.

[0020] The present application studies the antiviral effect of NM107 on IPNV, establishes a cell infection model and an animal infection model, and conducts drug treatment to explore the time, stage and treatment effect of drug action, and evaluates the inhibitory effect of NM107 on the replication of IPNV in vitro and in vivo. The results show that NM107 has an anti-IPNV effect at the cell level (in vitro) and the animal level (in vivo), and NM107 (Formula I) is a potential candidate drug for anti-IPNV infection. BRIEF DESCRIPTION OF DRAWINGS

[0021] Figure 1 NM107 inhibits the infection of CHSE-214 cells by IPNV. Among them, A is the relative expression level detection result of viral mRNA after NM107 treatment; B is the viral titer detection result after NM107 treatment. N.D. in the figure means not detected. In the figure, * indicates a significant difference (P<0.05) compared with the control group (PBS group).

[0022] Figure 2 Time-of-addition assay experiment. A is the time-of-addition NM107 administration sequence and administration time; B is the viral copy number after NM107 treatment at different times; C is the viral titer detection result after NM107 treatment at different times. In B and C, different lowercase letters indicate significant differences between each other (P<0.05).

[0023] Figure 3 NM107 inhibits viral RNA replication, but does not inhibit viral internalization or attachment. A is the effect of NM107 on viral vRNA at the viral attachment stage; B is the effect of NM107 on viral vRNA at the viral internalization stage; C is the effect of NM107 on viral vRNA at the viral replication stage; D is the effect of NM107 on viral mRNA at the viral replication stage. In the figure, * indicates significant difference (P<0.05); ns indicates no significant difference (P>0.05).

[0024] Figure 4NM107 inhibits rainbow trout IPNV infection (virus load). A is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 1 day after challenge; B is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 3 days after challenge; C is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 7 days after challenge; D is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 14 days after challenge. In the figure, * indicates significant difference (P < 0.05); ns indicates no significant difference (P > 0.05).

[0025] Figure 5 NM107 inhibits rainbow trout IPNV infection (virus load). A is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 1 day after challenge; B is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 3 days after challenge; C is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 7 days after challenge; D is the effect of different doses of NM107 on the relative expression level of viral mRNA in liver, spleen and head kidney 14 days after challenge. In the figure, * indicates significant difference (P < 0.05); ns indicates no significant difference (P > 0.05); N.D. indicates not detected. DETAILED DESCRIPTION

[0026] The present application will be further described in conjunction with the specific embodiments. The examples given are only for the purpose of illustrating the present application, and are not intended to limit the scope of the present application. The examples provided below can serve as a guide for further improvement by those of ordinary skill in the art, and do not in any way constitute a limitation on the present application.

[0027] The experimental methods in the following examples are all conventional methods, and are carried out according to the techniques or conditions described in the literature in the art or according to the product instructions, unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained commercially, unless otherwise specified.

[0028] Example 1, Application of NM107 in Anti-IPNV

[0029] I. Experimental materials

[0030] IPNV strain BJ2020-1 (GenBank Accession No. MW662108). Chinook salmon embryonic cell line (CHSE-214) (CRL-1681, ATCC) cell line was used for in vitro IPNV study. Cell culture medium MEM (C11095500BT), trypsin (C25200072), fetal bovine serum (FB25015), penicillin-streptomycin solution (C15140122) were purchased from Gibco; PrimeScript TM RT reagent Kit with gDNA Eraser (6210A), TB Green TM Premix Ex Taq TM II (Tli RNaseH Plus) (RR420A) were purchased from TaKaRa; Trizol reagent (10296028) was purchased from Invitrogen; Cell Counting Kit-8 (CCK-8) kit (B34304) was purchased from Bimake; NM107 (HY-10468) was purchased from MCE, the structural formula is as shown in formula I above. Rainbow trout was purchased from a farm with no record of IPNV detection in the past 5 years, and the fish was tested to confirm no IPNV. All animal experiments were conducted at Heilongjiang Fisher Research Institute of Chinese Academy of Fishery Sciences, in strict accordance with the guidelines of the Ethics Review Committee.

[0031] II. Experimental methods

[0032] 1. CC of NM107 cytotoxicity 50 and antiviral activity IC 50 detection

[0033] (1) CC 50 detection

[0034] The CHSE-214 cells in good growth state were added with trypsin for digestion and treatment, and then the CHSE-214 cells were inoculated into 96-well cell culture plates with 10% fetal bovine serum, 1% penicillin-streptomycin-containing MEM cell culture medium, with 1×10 4 The 96-well plates were placed in an 18℃ incubator for 24h, then fresh culture medium containing NM107 was added, with 7 concentration gradients of NM107, i.e. 100μM, 50μM, 25μM, 10μM, 5μM, 2.5μM, 0.5μM, and a control group without NM107 was set, and then cultured at 0.5% CO2 15℃ for 7d, and then the NM107 cytotoxicity was detected according to the recommended steps of the CCK-8 kit instruction manual.

[0035] The OD of NM107-treated cells 450 The drug concentration at which the value is reduced to 50% of that of the control cells is defined as the 50% cytotoxic concentration (CC 50 ) of NM107.

[0036] CC 50 is the drug concentration at which 50% of the cells are affected, and the higher the value, the lower the toxicity to the cells.

[0037] (2) IC 50 detection

[0038] CHSE-214 cells in 96-well plates were also treated with different concentrations of NM107, following the same procedure as in (1). Infection was carried out at 15°C for 1 h at an MOI of 0.1. After 7 days of incubation at 15°C in 0.5% CO2, the anti-viral activity of NM107 was detected using a CCK8 kit. The inhibition rate was calculated as [(NM107 OD 450 - viral control OD 450 ) / (control cell OD 450 - viral control OD 450 )] x 100%, and the 50% inhibitory concentration (IC 50 ) of NM107 against IPNV was calculated using regression analysis. In the calculation formula, "viral control" refers to cells that were only infected with the virus, and "control cell" refers to cells that were normally cultured with the culture medium.

[0039] IC 50 refers to the drug concentration that can effectively inhibit 50% of the cells from being infected with the virus, and the smaller the value, the better the inhibitory effect on the virus.

[0040] (3) Calculation of SI

[0041] SI: Selectivity index, which is the ratio of CC 50 to IC 50 , and the larger the value, the higher the possibility of the drug.

[0042] 2. Inhibition of NM107 on IPNV in CHSE-214 cells

[0043] CHSE-214 cells were seeded into 6-well plates at a density of 1 x 10 5 / well, cultured to approximately 90% density per well. One hour after IPNV infection (MOI = 0.1), cells were treated with 5 μM NM107 and cultured at 15°C in a 0.5% CO2 incubator for 24 h and 48 h. Cells and supernatant were then collected to detect intracellular viral replication (viral mRNA level, see step 6 for details) and extracellular viral titer (see step 7 for details) of IPNV after NM107 treatment.

[0044] 3. Time-of-addition assay experiment

[0045] CHSE-214 cells were seeded into 6-well plates at a density of 1×10⁶ cells / well. 5 Cells were cultured in each well to approximately 90% confluence. Cells were treated with NM107 (MOI 0.1) before, during, or after IPNV infection. IPNV infection was defined as 0 h, and cells were treated with 5 μM NM107 at -8, -4, -2, 0, 2, 4, and 8 h. Cells and culture supernatant were collected after 48 h, and total RNA was extracted to detect viral copy number. Specifically, quantitative real-time PCR of mRNA was performed (see step 6 for details), and a standard curve was established to calculate the viral copy number. The culture supernatant was serially diluted to determine the viral titer (see step 7 for details). Cells cultured in standard culture medium were used as a control group.

[0046] 4. Viral attachment, internalization, and RNA replication

[0047] CHSE-214 cells were seeded into 6-well plates at a density of 1×10⁶ cells / well. 5 / well, cultured to approximately 90% density per well. In the virus attachment assay, cells were incubated with IPNV (MOI = 10.0) and 5 μM NM107 at 4°C for 1 h, then washed with PBS, and the treated cells were collected. In the virus internalization assay, cells were incubated with IPNV (MOI = 10.0) at 4°C for 1 h, the old culture medium was discarded, washed twice with cold PBS, 5 μM NM107 was added, and the cells were cultured at 15°C for 1 h. After treatment with pre-chilled pH 3.0 sodium citrate buffer for 30 s, the medium was discarded, washed with PBS, and the cells were collected. In the RNA replication assay, cells were infected with IPNV (MOI = 10.0) at 4°C for 1 h, the old culture medium was discarded, washed twice with pre-chilled PBS, and cultured at 15°C for 2 h. After adding 5 μM NM107, the cells were cultured for another 4 h, and the cells were collected. The viral RNA expression level was detected by real-time quantitative PCR (RT-qPCR) (see step 6 for details).

[0048] 5. Determination of viral load in rainbow trout

[0049] To determine the antiviral effect of NM107 in vivo in rainbow trout, rainbow trout with an average weight of 5±1 g were infected with IPNV. 300 healthy rainbow trout with an average weight of 5±1 g were selected, acclimated to the laboratory environment at 12℃ for 2 weeks, and fed with dry granular feed at will before the test. The 300 healthy rainbow trout were randomly divided into 6 groups, 50 in each group: PBS group: after feeding normal feed for 5 days, intraperitoneal injection of phosphate buffer solution (PBS, 50 μL / tail) as negative control; P group: after feeding normal feed for 5 days, intraperitoneal injection of IPNV (2×10 6 TCID 50 / tail, 50 μL) as positive control; 10 group and 50 group: feeding feed containing NM107 (10 or 50 mg / kg body weight) for 5 days, and injecting PBS (PBS, 50 μL / tail); 10+P group and 50+P group: feeding feed containing NM107 at 10 or 50 mg / kg body weight for 5 days before infection, and injecting IPNV (2×10 6 TCID 50 / tail, 50 μL). At 1, 3, 7 and 14 days after IPNV infection, liver, spleen and head kidney were collected to determine viral titer and load (see steps 6 and 7 for details).

[0050] 6. Viral load determination

[0051] Trizol reagent (Invitrogen, Shanghai, China) was used to extract viral RNA. PrimeScript TM RT reagent Kit with gDNA Eraser (6210A) was used for reverse transcription to obtain cDNA according to the instructions. Then the obtained cDNA was used as a template, and TB Green TM Premix Ex Taq TM II (Tli RNaseH Plus) kit (RR420A) was used for qPCR according to the instructions. The primers used for RT-qPCR are shown in Table 1, and 2 -ΔΔCT Methods were used to calculate the relative expression of the target gene.

[0052] Table 1, IPNV RNA determination primers

[0053]

[0054] Note: β-actin is the internal reference gene, vRNA F is the gene sequence inserted during reverse transcription into cDNA, and vRNA R and vRNA tag are the primers used in quantitative PCR (the vRNA F sequence contains the vRNA tag, which is a sequence not present in the designed viral genome; therefore, the relative expression level of the vRNA tag during quantitative PCR can represent the relative expression level of vRNA). Similarly, mRNA R is the gene sequence inserted during reverse transcription into cDNA, and mRNA F and mRNA tag are the primers used in quantitative PCR.

[0055] 7. Titer determination

[0056] The infection titers of the tested tissues and cell culture supernatants were determined using standard methods on CHSE-214 monolayer cells. 10 [cells were inoculated]. 1 10 2 10 3 10 4 10 5 10 6 10 7 10 8 10 9 Culture supernatant was prepared at each dilution, with 100 μL per well for every 8 wells. A blank control group was also included. After 7 days of incubation at 15°C and 0.5% CO2, the TCID was calculated using the Reed-Muench method. 50 TCID cell culture suspension 50 Represented as TCID 50 / mL, TCID of tissue sample 50 Represented as TCID 50 / g.

[0057] III. Results and Analysis

[0058] 1. NM107 is an effective antiviral drug for IPNV.

[0059] Previous reports have indicated that NM107 has an IC50 effect against human norovirus (HG23 cells). 50 The value was 18±4 μM, and the IC50 value against DENV (Huh-7 cells) was 18±4 μM. 50 The value was 31.4 ± 0.5 μM, and the IC50 against feline coronavirus (CRFK cells) was [value missing]. 50 The value is 2.7-5.3 μM. This invention detects the IC of NM107 for IPNV. 50 The results showed that NM107 has anti-IPNV activity. NM107 also showed activity against CC in CHSE-214 cells. 50 For ICs with a wavelength >50μM, the IPNV value is [value missing]. 50 The value is 1.374 μM, and SI = CC is calculated.50 / IC 50 >36.4. These results indicate that NM107 has anti-IPNV activity and is not cytotoxic.

[0060] 2. NM107 inhibits the infection of CHSE-214 cells with IPNV.

[0061] To further evaluate the anti-IPNV effect of NM107, this invention detected intracellular viral replication and extracellular viral titer of IPNV after NM107 treatment. Compared with the PBS control group, the viral RNA expression level after NM107 treatment decreased by 200-fold (24h) and 892-fold (48h), respectively. Figure 1 (A), and the viral titer after NM107 treatment could not be detected at 24h, and the viral titer decreased by 5.5 log(A) at 48h. Figure 1 (Middle B). Therefore, NM107 significantly inhibited IPNV infection of CHSE-214 cells.

[0062] 3. NM107 can inhibit IPNV infection before, during, and after infection.

[0063] To determine the exact time when NM107 exerts its antiviral effect, this invention conducted a time-of-addition assay. Figure 2 NM107 was added before IPNV infection (-8, -4, or 2 hours), during infection (0 hours), or after infection (2, 4, or 8 hours). Pretreatment with NM107 significantly inhibited IPNV infection, reducing viral copy numbers by 2.84-fold (-8 hours), 1.75-fold (-4 hours), and 1.58-fold (-2 hours), respectively. Figure 2 (B) The viral titers were 10. - 3.1 TCID 50 / mL (-8 hours), 10 -5.7 TCID 50 / mL (-4 hours) and 10 -5.3 TCID 50 / mL (-2 hours), all were lower than the control group (10 -7.5 TCID 50 / mL)( Figure 2 (C). The viral copy number and viral titer co-treated with NM107 were both lower than those in the control group (C). Figure 2 China B and Figure 2 (C). Post-treatment with NM107 also significantly suppressed viral copy number and viral titer (C). Figure 2 China B and Figure 2NM107 inhibited IPNV infection before, during and after IPNV infection.

[0064] 4. NM107 inhibits viral RNA replication, but not viral internalization or attachment

[0065] Viruses must attach, internalize into cells and replicate within cells for efficient infection. To further determine the stage at which NM107 blocks IPNV infection, the present application detected viral RNA levels at the stages of viral attachment, internalization and replication. NM107 did not alter the relative expression levels of viral RNA at the stages of viral attachment and internalization into cells ( Figure 3 Mids A and Figure 3 Mids B), but significantly inhibited the relative expression levels of viral vRNA and mRNA at the stage of viral replication ( Figure 3 Mids C and Figure 3 Mids D). In the viral replication experiment, the relative expression level of viral vRNA was reduced by 3.32-fold at 4 h post-treatment with NM107 ( Figure 3 Mids C), and the relative expression level of viral mRNA was reduced by 40-fold ( Figure 3 Mids D). Thus, NM107 blocks IPNV RNA replication, but not viral internalization and attachment.

[0066] 5. NM107 inhibits IPNV infection in rainbow trout

[0067] To further investigate the antiviral effect of NM107 on IPNV, the present application evaluated the protective effect of NM107 on rainbow trout by detecting viral load in the liver, spleen and head kidney of rainbow trout. At 1 day post-IPNV infection, 50 mg / kg NM107 significantly reduced the relative expression level of IPNV mRNA in the liver, spleen or head kidney, while 10 mg / kg NM107 did not significantly inhibit the relative expression level of IPNV mRNA in the liver, spleen or head kidney ( Figure 4 Mids A). At 3 days post-IPNV infection, 50 mg / kg NM107 reduced the relative expression level of IPNV mRNA in the liver, spleen and head kidney; 10 mg / kg NM107 reduced the relative expression level of IPNV mRNA in the spleen and head kidney, but had no effect on the relative expression level of IPNV mRNA in the liver ( Figure 4 Mids B). At 7 days and 14 days post-IPNV infection, both 10 mg / kg and 50 mg / kg NM107 reduced the relative expression level of IPNV mRNA in the liver, spleen and head kidney ( Figure 4 Mids C and Figure 4 Mids D).

[0068] In addition, viral titers in the liver, spleen, and head kidney were measured at 1, 3, 7, and 14 days post-IPNV infection. At 1 day post-IPNV infection, the IPNV viral titer in the liver was 10. -4.2 TCID 50 / g (50+P group), lower than P group (10 -7.0 TCID 50 / g), but there was no significant difference between the 10+P group and the P group ( Figure 5 (A) At 3 days post-IPNV infection, the IPNV viral titer in the liver was 10. - 4.2 TCID 50 / g (50+P group), lower than P group (10 -6.5 TCID 50 / g), but there was no significant difference between the 10+P group and the P group ( Figure 5 (B) ; Seven days after IPNV infection, the IPNV viral titer in the liver was 10 -3.2 TCID 50 / g(10+P group) and 10 - 2.5 TCID 50 / g (50+P group) was lower than that of P group (10) -5.0 TCID 50 / g)( Figure 5 (C) ; No viral titer was detected in the liver 14 days after IPNV infection ( Figure 5 (D). Meanwhile, one day after IPNV infection, the IPNV viral titer in the spleen was 10. -4.5 TCID 50 / g (50+P group), lower than P group (10 -7.0 TCID 50 / g), but there was no significant difference between the 10+P group and the P group ( Figure 5 (A) At 3 days post-IPNV infection, the IPNV viral titer in the spleen was 10. -4.0 TCID 50 / g(10+P group) and 10 -3.8 TCID 50 / g (50+P group) was lower than that of P group (10) -6.0 TCID 50 / g)( Figure 5 (B) ; Seven days after IPNV infection, the IPNV viral titer in the spleen was 10 -3.0 TCID 50 / g(10+P group) and 10 -2.0 TCID 50 / g (50+P group) was lower than that of P group (10)-5.0 TCID 50 / g)( Figure 5 Medium C); no virus titers were detected in the spleen at 14 days post IPNV infection (Medium D). Similar results were also found in the head kidney, indicating that NM107 can significantly inhibit IPNV virus proliferation in the rainbow trout body. Figure 5

[0069] In addition, the results of the relevant detection indexes of the 10th and 50th groups (to prove that the NM107 feeding of rainbow trout at two doses alone has no toxic effect) showed no change compared with the ordinary feed group (i.e. the PBS group).

[0070] The above has been described in detail. For those skilled in the art, without departing from the purpose and scope of the present application, and without unnecessary experiments, the present application can be implemented in a wider range under equivalent parameters, concentrations and conditions. Although the present application gives a special example, it should be understood that the present application can be further improved. In summary, according to the principle of the present application, this application intends to include any change, use or improvement of the present application, including the change made by the conventional technology known in the art, which is out of the range disclosed in the present application.​

Claims

1. Use of NM107 or a pharmaceutically acceptable salt thereof or a substance having NM107 or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for use against infectious pancreatic necrosis virus.

2. Use of NM107 or a pharmaceutically acceptable salt thereof or a substance having NM107 or a pharmaceutically acceptable salt thereof as an active ingredient in the preparation of a product for use in the prevention and / or treatment of a disease caused by infection with infectious pancreatic necrosis virus.

3. Use according to claim 2, characterized in that: The disease is infectious pancreatic necrosis.

4. Use according to any one of claims 1 to 3, characterized in that: The product is capable of reducing the expression of infectious pancreatic necrosis virus RNA at the level of fish cells.

5. Use according to claim 4, characterized in that: The fish cells are salmon embryo cells.

6. Use according to any one of claims 1 to 3, characterized in that: The product is capable of reducing the expression of infectious pancreatic necrosis virus RNA at the level of fish.

7. Use according to claim 6, characterized in that: The fish is a fish that can be infected with infectious pancreatic necrosis virus.

8. Use according to claim 7, characterized in that: The fish is rainbow trout.

9. Use according to any one of claims 1 to 3, characterized in that: The product is capable of reducing the infectious pancreatic necrosis virus titer at the level of fish cells.

10. Use according to claim 9, characterized in that: The fish cells are salmon embryo cells.

11. Use according to any one of claims 1 to 3, characterized in that: The product is capable of reducing the infectious pancreatic necrosis virus titer at the level of fish.

12. Use according to claim 11, characterized in that: The fish is a fish that can be infected with infectious pancreatic necrosis virus.

13. Use according to claim 12, characterized in that: The fish is rainbow trout.

14. The use according to any one of claims 1 to 3, characterized in that: The NM107 is a compound represented by Formula I; Formula I.

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