Use of salicylamide derivatives for the preparation of anti-small rna virus drugs

Abstract

This invention relates to the application of salicylamide derivatives in the preparation of anti-small RNA virus drugs, belonging to the field of antiviral drug technology. This invention discloses the application of salicylamide and / or its derivatives in the preparation of anti-small RNA virus drugs. Through various experimental methods, this invention confirms that niclosamide and its derivatives HJW1107 and CZY1111 can significantly inhibit the early infection and replication of small RNA viruses such as EMCV, EV-D68, and CVA10, inhibit virus-induced cytopathic effects, and enhance the survival rate of infected cells. This indicates that niclosamide and its derivatives HJW1107 and CZY1111 have broad-spectrum antiviral activity and can be used to prepare therapeutic drugs against small RNA virus infections, thereby preventing and treating diseases caused by small RNA viruses, and has good clinical application prospects.

Description

Technical Field

[0001] This invention relates to the field of antiviral drug technology, and in particular to the application of salicylamide derivatives in the preparation of anti-small RNA virus drugs. Background Technology

[0002] Picornaviridae ( Picornaviridae Picornaviridae (PRNAviridae) includes a variety of viruses that are of significant pathogenicity to humans and animals, such as encephalomyocarditis virus (EMCV), enterovirus D68 (EV-D68), and Coxsackievirus A10 (CVA10). These viruses can cause a range of clinical symptoms, from mild respiratory infections to severe neurological disorders. EV-D68 is closely associated with neurological diseases such as acute flaccid myelitis (AFM), while CVA10 is one of the important pathogens of hand-foot-and-mouth disease. Despite the wide prevalence and high pathogenicity of these viruses, there are currently no specific antiviral drugs for PRNAviridae infections.

[0003] Most existing antiviral drugs are inhibitors developed targeting specific viral sites, which have limitations such as limited efficacy, high host toxicity, and a tendency to induce drug resistance mutations. For example, drugs targeting enteroviruses, such as pleconaril, have entered clinical trials, but their use has been limited due to low bioavailability and the frequent emergence of drug-resistant strains. Therefore, developing novel broad-spectrum antiviral drugs that can target conserved viral structures or host-dependent factors has significant clinical translational value.

[0004] Niclosamide is an approved oral antiparasitic drug for the treatment of tapeworm infections with a good safety record. Recent studies have shown that niclosamide exhibits antiviral activity in in vitro and in vivo models, targeting various viral families, such as coronaviruses, flaviviruses, and influenza viruses. Its mechanism of action may be related to inhibiting viral entry, interfering with endocytosis, regulating host signaling pathways (such as Wnt / β-catenin, NF-κB), or acting on the viral replication complex. However, research on its antiviral activity and application against pituitary viruses (including EMCV, EV-D68, CVA10, etc.) remains very limited, and its potential as a broad-spectrum antiviral drug against pituitary viruses has not yet been fully explored. Therefore, exploring the inhibitory effects of niclosamide and its derivatives on pituitary virus infections and developing novel antiviral strategies based on this drug has significant scientific importance and promising clinical application prospects. Summary of the Invention

[0005] The purpose of this invention is to overcome the shortcomings of the prior art and provide the application of salicylamide derivatives in the preparation of anti-small RNA virus drugs.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides the use of salicylamide and / or its derivatives in the preparation of anti-small RNA virus drugs.

[0007] This invention systematically evaluated the inhibitory effects of niclosamide and its derivatives on various small RNA viruses and revealed their mechanism of action, providing novel antiviral strategies and theoretical basis for the development of anti-small RNA virus drugs.

[0008] Furthermore, the derivatives include compounds HJW1107 and / or CZY1111, the chemical structural formula of compound HJW1107 is shown in Formula II, and the chemical structural formula of compound CZY1111 is shown in Formula V: Formula II; Formula V.

[0009] Furthermore, the small RNA virus includes at least one of enterovirus D68, coxsackievirus A10, and encephalomyocarditis virus.

[0010] Furthermore, the drug is a drug that inhibits the infection and proliferation of small RNA viruses.

[0011] Furthermore, the drug also includes pharmaceutically acceptable excipients and carriers.

[0012] Furthermore, the drug is in the form of tablets, granules, pills, capsules, injections, or dispersants.

[0013] In a second aspect, the present invention provides the use of salicylamide and / or its derivatives in the preparation of medicaments for the prevention and / or treatment of diseases caused by small RNA viruses.

[0014] Furthermore, the drug is a drug for the prevention and / or treatment of respiratory diseases and / or acute flaccid myelitis caused by enterovirus D68.

[0015] Furthermore, the drug is for the prevention and / or treatment of hand-foot-mouth disease caused by Coxsackievirus A10.

[0016] Furthermore, the drug is for the prevention and / or treatment of myocarditis and / or encephalitis caused by encephalomyocarditis virus.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention, through various experimental methods, demonstrates that niclosamide and its derivatives HJW1107 and CZY1111 can significantly inhibit the early infection and replication of small RNA viruses such as EMCV, EV-D68, and CVA10. It also inhibits the cytopathic effects induced by EMCV, EV-D68, and CVA10 viruses and enhances the survival rate of infected cells. These findings indicate that niclosamide and its derivatives HJW1107 and CZY1111 possess broad-spectrum antiviral activity and can be used to prepare therapeutic drugs against small RNA virus infections, thereby preventing and treating diseases caused by small RNA viruses, and showing promising clinical application prospects. Attached Figure Description

[0018] Figure 1 This describes a method for preparing compound HJW1107.

[0019] Figure 2 This describes the preparation method of compound CZY1111.

[0020] Figure 3 The study investigated the inhibitory effects of niclosamide and its derivatives HJW1107 and CZY1111 on the infection rates of EMCV, EV-D68, and CVA10 viruses. In this study, A represents EMCV virus; B represents EV-D68 virus; and C represents CVA10 virus.

[0021] Figure 4 IC50 assays for the inhibition of EV-D68, EMCV, and CVA10 viral infections by niclosamide and its derivatives HJW1107 and CZY1111 50 Where A represents the IC50 of niclosamide against EV-D68 virus infection. 50 B represents the IC50 of compound HJW1107 against EV-D68 virus infection. 50 C represents the IC50 of compound CZY1111 against EV-D68 virus infection. 50 D represents the IC50 of niclosamide against EMCV virus infection. 50 E represents the IC50 value of compound HJW1107 against EMCV virus infection. 50 F represents the IC50 of compound CZY1111 against EMCV virus infection. 50 G represents the IC50 of niclosamide against CVA10 virus infection. 50 H represents the IC50 of compound HJW1107 against CVA10 virus infection. 50 I represents the IC50 of compound CZY1111 against CVA10 virus infection. 50 .

[0022] Figure 5The effects of niclosamide and its derivatives HJW1107 and CZY1111 on the multi-step growth of EMCV virus were investigated. In this study, A represents niclosamide; B represents compound HJW1107; and C represents compound CZY1111.

[0023] Figure 6 The effects of niclosamide and its derivatives HJW1107 and CZY1111 on late-stage replication of EMCV virus were investigated. In this study, A represents niclosamide; B represents compound HJW1107; and C represents compound CZY1111.

[0024] Figure 7 The inhibitory effects of niclosamide and its derivatives HJW1107 and CZY1111 on EV-D68 virus at different time points were investigated. In this study, A represents niclosamide; B represents compound HJW1107; and C represents compound CZY1111. Detailed Implementation

[0025] To better illustrate the purpose, technical solution, and advantages of this invention, the invention will be further described below with reference to specific embodiments. Unless otherwise specified, other materials and reagents used in the embodiments are commercially available.

[0026] Example 1: N-(2-chloro-4-(trifluoromethyl)phenyl)-2-hydroxy-5-methylbenzamide (HJW1107) 1. Preparation of compound HJW1105 The preparation reaction method of compound HJW1107 is as follows: Figure 1 As shown, a mixture of 2-methoxy-5-methylbenzoic acid (254 mg, 1.53 mmol) and 2-chloro-4-(trifluoromethyl)aniline (300 mg, 1.53 mmol) was dissolved in 25 mL of toluene, and then phosphorus trichloride (316 mg, 2.30 mmol) was added at room temperature to obtain a mixture. The mixture was stirred at 100 °C for 6 h to obtain a reaction solution. The reaction solution was diluted with dichloromethane (20 mL), washed successively with distilled water (10 mL) and saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate. The concentrate was slurried with methanol (10 mL), and the amide intermediate HJW1105 was separated by filtration as a white solid (510 mg, yield 97%).

[0027] The 1H NMR data for HJW1105 are as follows: 1 H NMR (500 MHz, Chloroform- d ) δ 10.84 (s, 1H), 8.88 (d, J = 8.7 Hz, 1H), 8.10 (d,J = 2.2 Hz, 1H), 7.57 (d, J = 8.5 Hz, 1H), 7.34 (dt, J = 8.5, 2.2 Hz, 1H), 6.96 (dd, J = 8.4, 1.8 Hz, 1H), 4.07 (d, J = 1.8Hz, 3H), 2.37 (d, J = 1.8 Hz, 3H).

[0028] The chemical structural formula of HJW1105 is shown in Formula I: Formula I.

[0029] 2. Preparation of compound HJW1107 HJW1105 (477 mg, 1.39 mmol) was dissolved in 20 mL of dichloromethane, and boron tribromide (1042 mg, 4.16 mmol) was added dropwise at -10 °C to obtain a mixture. The mixture was stirred at room temperature for 2 h to obtain a reaction solution. The reaction solution was diluted with dichloromethane (30 mL), washed successively with distilled water (20 mL) and saturated brine (20 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate. The concentrate was slurried with methanol (10 mL), and separated by filtration to obtain a white solid compound HJW1107 (449 mg, yield 98.3%).

[0030] The 1H NMR spectrum data of compound HJW1107 are as follows: 1 H NMR (500 MHz, DMSO- d 6) δ 11.79 (s,1H), 11.22 (s, 1H), 8.76 (d, J = 8.7 Hz, 1H), 7.97 (d, J = 2.2 Hz, 1H), 7.84 (d, J = 2.4 Hz, 1H), 7.79 - 7.66 (m, 1H), 7.37 - 7.20 (m, 1H), 6.96 (d, J = 8.3 Hz, 1H), 2.28 (s, 3H).

[0031] The carbon NMR data of compound HJW1107 are as follows: 13C NMR (151 MHz, DMSO-d6)δ164.0, 154.1,139.2, 134.9, 130.9, 128.7, 126.4 (d, J = 4.1 Hz), 125.2 (d, J = 4.0 Hz), 124.5 (q, J = 32.8 Hz), 123.5 (q, J = 272.0 Hz), 122.8, 121.7, 117.6, 117.0,20.0.

[0032] The high-resolution mass spectrometry data of compound HJW1107 are as follows: HRMS (ESI) calcd for C 15 H 10 ClF3NO3344.0307 (MH)-, found 344.0309.

[0033] The high-performance liquid chromatography purity of compound HJW1107 was 99.6%. t R = 14.6 min).

[0034] The chemical structural formula of compound HJW1107 is shown in Formula II: Formula II.

[0035] Example 2 N-(2-(3-bromopropoxy)-4-nitrophenyl)-5-chloro-2-hydroxybenzamide (CZY1111) 1. Preparation of compound CZY1107 like Figure 2 As shown, a mixture of 2-amino-5-nitrophenol (600 mg, 3.89 mmol) and potassium carbonate (1614 mg, 11.68 mmol) was dissolved in 10 mL of acetonitrile, and then 1,3-dibromopropane (1571 mg, 7.79 mmol) was added at room temperature to obtain a mixture. The mixture was stirred at 60 °C for 12 h to obtain a reaction solution. The reaction solution was diluted with ethyl acetate (100 mL), washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate. The concentrate was purified by silica gel column chromatography (petroleum ether:ethyl acetate = 10:1, v / v) to give a pale yellow oil product CZY1107 (509 mg, yield 47%).

[0036] The 1H NMR spectrum data for CZY1107 are as follows: 1H NMR (500 MHz, CDCl3) δ 7.82 (dd, J = 8.7, 2.4Hz, 1H), 7.69 (d, J = 2.4 Hz, 1H), 6.65 (d, J = 8.7 Hz, 1H), 4.55 (s, 2H), 4.25(t, J = 5.9 Hz, 2H), 3.60 (t, J = 6.4 Hz, 2H), 2.41 (p, J = 6.1 Hz, 2H).

[0037] The chemical structural formula of CZY1107 is shown in Formula III: Formula III.

[0038] 2. Preparation of compound CZY1110 A mixture of a pale yellow oily product CZY1107 (150 mg, 0.54 mmol) and 5-chloro-2-methoxybenzoic acid (152 mg, 0.81 mmol) was dissolved in 10 mL of toluene, and then phosphorus trichloride (112.32 mg, 0.82 mmol) was added at room temperature to obtain a mixture. The mixture was stirred at 100 °C for 5 h to obtain a reaction solution. The reaction solution was diluted with dichloromethane (20 mL), washed successively with distilled water (10 mL) and saturated brine (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate. The concentrate was slurried with 10 mL of methanol, and the amide intermediate CZY1110 was separated by filtration as a pale yellow solid (232 mg, yield 96%).

[0039] The 1H NMR data for CZY1110 are as follows: 1 H NMR (500 MHz, DMSO- d 6) δ 9.75 (s, 1H), 7.85 (d, J = 9.0 Hz, 1H), 7.14 (d, J = 2.9 Hz, 1H), 7.14-7.11 (m, 1H), 7.04 (d, J = 2.6Hz, 1H), 6.83 (dd, J = 8.9, 2.9 Hz, 1H), 6.52 (d, J = 8.9 Hz, 1H), 3.56 (t, J= 6.1Hz, 2H), 3.23 (s, 3H), 2.90 (t, J = 6.7 Hz, 2H), 1.59 (p, J = 6.4 Hz, 2H).

[0040] The chemical structural formula of CZY1110 is shown in Formula IV: Formula IV.

[0041] 3. Preparation of compound CZY1111 The amide intermediate CZY1110 (150 mg, 0.34 mmol) was dissolved in 10 mL of dichloromethane, and boron tribromide (338.79 mg, 1.35 mmol) was added dropwise at -10 °C to obtain a mixture. The mixture was heated to 0 °C and stirred for 10 min. The reaction was monitored by thin-layer chromatography until complete, and the reaction solution was obtained. The reaction solution was diluted with 20 mL of dichloromethane, washed with 10 mL of water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a concentrate. The concentrate was slurried with 10 mL of methanol, and separated by filtration to obtain a yellow solid compound CZY1111 (115 mg, yield 79%).

[0042] The 1H NMR spectrum data of compound CZY1111 are as follows: 1 H NMR (500 MHz, DMSO- d 6) δ 12.14 (s,1H), 11.21 (s, 1H), 8.72 (d, J = 9.0 Hz, 1H), 7.97 (dd, J = 7.3, 2.6 Hz, 2H), 7.88 (d, J = 2.5 Hz, 1H), 7.52 (dd, J = 8.7, 2.9 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 4.36 (t, J = 6.0 Hz, 2H), 3.75 (t, J = 6.4 Hz, 2H), 3.17 (s, 2H), 2.41 (p, J = 6.2Hz, 2H).

[0043] The carbon NMR data of compound CZY1111 are as follows: 13 C NMR (151 MHz, DMSO- d6) δ 162.2,154.9, 147.0, 142.6, 134.3, 133.6, 130.1, 123.8, 120.0, 119.2, 118.5, 117.5,106.3, 67.2, 31.5, 31.1.

[0044] The high-resolution mass spectrometry data for compound CZY1111 are as follows: HRMS (ESI) calcd for C 16 H 13 BrClN2O 5, 426.9702 (MH) - , found, 426.9703. .

[0045] The high-performance liquid chromatography purity of compound CZY1111 is 98.7%. t R = 9.51 min).

[0046] The chemical structural formula of CZY1111 is shown in Formula V: Formula V.

[0047] Example 3: Determination of the inhibitory effects of niclosamide and its derivatives HJW1107 and CZY1111 on various small RNA viruses and their IC50 values. 50 1. Detection of the effects of niclosamide and its derivatives HJW1107 and CZY1111 on single-round replication of various small RNA viruses. A549 cells were fed at a rate of 1.5 × 10⁻⁶. 4 A549 cells were seeded in 96-well plates and cultured at 37°C in a 5% CO2 incubator for 16–18 h. Two h before viral infection, niclosamide and its derivatives HJW1107 and CZY1111 (1 μM) were added to the cells, while the control group received the same volume of DMSO (three replicates for each experimental condition). Eight h after viral infection, the proportion of infected virus antigen-positive cells was detected by flow cytometry. The MOI for EMCV, EV-D68, and CVA10 was 1.

[0048] The antiviral activity of the compounds was expressed as the inhibition rate of viral replication, as shown in Tables 1, 2, and 3. The calculation formula is as follows: Inhibition rate (%) = (1 - Proportion of virus-positive cells in the compound group / Proportion of virus-positive cells in the blank control group) × 100%. Niclosamide and its derivatives HJW1107 and CZY1111 significantly inhibited the infection of EMCV, EV-D68, and CVA10. The inhibition rates of niclosamide, HJW1107, and CZY1111 against EMCV were 62.38±0.11%, 77.14%±1.91%, and 49.59%±7.66%, respectively. The inhibition rates of niclosamide and its derivatives HJW1107 and CZY1111 against EV-D68 were 68.25%±0.66%, 57.98%±9.01%, and 68.81%±0.70%, respectively. The inhibition rates of niclosamide and its derivatives HJW1107 and CZY1111 against CVA10 were 79.10%±3.31%, 50.97%±4.31%, and 49.12%±1.72%, respectively. Figure 3 A to Figure 3 C). The IC50 of niclosamide and its derivatives HJW1107 and CZY1111 against EMCV 50 The values ​​were 1.149 μM, 0.762 μM, and 0.947 μM; for the IC of EV-D68 50 The values ​​were 0.674 μM, 1.46 μM, and 0.599 μM; for CVA10 IC 50 are 0.995 μM, 1.358 μM, 0.999 μM ( Figure 4 A to Figure 4 I).

[0049] Table 1. Inhibition rate of EMCV virus replication at 1 μM Table 2. Inhibition rate of EV-D68 virus replication at 1 μM Table 3. Inhibition rate of CVA10 virus replication at 1 μM 2. Detection of the effects of niclosamide and its derivatives HJW1107 and CZY1111 on multiple rounds of replication of various small RNA viruses. (1) EMCV multi-step growth curve In a 12-well plate, 3 × 10⁻⁶ ppm are used per well. 5A549 cells were seeded at a density of 3 cells / well (3 replicates per experimental condition) and cultured overnight at 37°C in a 5% CO2 incubator. Two hours before viral infection of A549 cells, 1 μM niclosamide and its derivatives HJW1107 and CZY1111 were added to the cells, with an MOI of 0.01. The inoculation solution contained 1 μM niclosamide and its derivatives HJW1107 and CZY1111. Inoculation was continued for 1 hour. After infection, the viral solution was discarded, and the cells were washed 5 times with preheated DMEM medium. Then, 1 mL of DMEM maintenance medium containing 2% (v / v) FBS was added to each well for continued culture. Cell supernatant was collected at 12 h, 24 h, and 48 h post-infection for subsequent viral titer detection.

[0050] (2) EMCV virus titer detection BHK-21 cells were administered at a rate of 1×10⁻⁶. 6 Cells were seeded into each well of a 6-well plate and incubated at 37°C in a 5% CO2 incubator for 16–18 h. The next day, the collected supernatant was serially diluted with DEME medium containing 0.01% (v / v) BSA to obtain the absorbed supernatant. The medium in the cell culture plate was then discarded, and starting from the highest dilution, 0.4 mL of the diluted supernatant was seeded into each well (two replicates per dilution). The culture plate was incubated at 37°C for 1 h, manually agitated every 15 min.

[0051] During adsorption, prepare the immobilized agarose gel: mix 1.6% (w / v) agarose (55°C) with an equal volume of 2×MEM medium (37°C) containing 2% (v / v) FBS to obtain the agarose gel.

[0052] After adsorption, starting with the highest dilution well, add 4 mL of agarose gel to each well and allow it to solidify at room temperature. Then, incubate the cell culture plate in a 37°C CO2 incubator for 2 days. After the fourth day of incubation, fix the cells with 4% (w / v) paraformaldehyde as the fixative. After fixation, remove the fixative and agarose gel, and add 2 mL of 1% (w / v) crystal violet to each well for 10 min. After staining, wash away any remaining dye, dry, and then photograph to count the number of viral plaques.

[0053] The results showed that niclosamide and its derivatives HJW1107 and CZY1111 could inhibit multiple rounds of EMCV replication. At 24 h and 48 h, the viral titer in the niclosamide-treated group was two orders of magnitude lower than that in the control group. At 24 h and 48 h, the viral titer in the HJW1107-treated group was one order of magnitude lower than that in the control group. At 24 h, the viral titer in the CZY1111-treated group was one order of magnitude lower than that in the control group. Figure 5 ).

[0054] Example 4: Niclosamide and its derivatives HJW1107 and CZY1111 act on the early stages of viral replication. (1) Investigation of the effects of niclosamide and its derivatives HJW1107 and CZY1111 on late viral replication by transfecting viral RNA with liposomes EMCV genomic RNA was extracted from EMCV virus using the phenol-chloroform extraction method. For RNA transfection, A549 cells were cultured at a density of 1 × 10⁶ cells per well. 5 Cells were seeded at a density of 1000 μM in 24-well plates. Sixteen h after seeding, 2 h before transfection, niclosamide and its derivatives HJW1107 and CZY1111 (1 μM) were added to the cells, and transfection was performed using 1.6 μg of EMCV RNA following the Lipofectamine 3000 reagent manufacturer's instructions. Ten h after transfection, the cell culture supernatant was collected, and viral titers were subsequently determined on BHK-21 cells using the plaque assay described in Example 3.

[0055] The results showed that niclosamide and its derivatives HJW1107 and CZY1111 had no effect on the RNA replication, composition, and release of EMCV virus, indicating that niclosamide and its derivatives HJW1107 and CZY1111 do not act on the replication and late stages of EMCV virus. Figure 6 ).

[0056] (2) Observation of virus infection inhibition at different time points after drug administration A549 cells were divided into 1.5 × 10⁻⁶ cells. 4Cells were seeded in 96-well plates at 37°C and cultured in a 5% CO2 incubator for 16–18 h. EV-D68 was then used to infect A549 cells with an MOI of 1. The experimental groups were as follows: Cells were treated with 1 μM niclosamide and its derivatives HJW1107 and CZY1111 before EV-D68 infection, with continuous drug administration. After 1 h of infection, 1 μM niclosamide and its derivatives HJW1107 and CZY1111 were added. After 2 h of infection, 1 μM niclosamide and its derivatives HJW1107 and CZY1111 were added. After 4 h of infection, 1 μM niclosamide and its derivatives HJW1107 and CZY1111 were added. The control group received the same volume of DMSO (three replicates were set for each experimental condition). After 8 h of infection, the proportion of EV-D68-infected positive cells was detected by flow cytometry.

[0057] The results showed that niclosamide and its derivatives HJW1107 and CZY1111 had the highest inhibitory efficiency when administered 2 hours before infection, and the inhibitory efficiency gradually decreased with the time of administration, indicating that niclosamide and its derivatives HJW1107 and CZY1111 act on the early stage of viral infection. Figure 7 ).

[0058] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. Application of salicylamide and / or its derivatives in the preparation of anti-small RNA virus drugs.

2. The application as described in claim 1, characterized in that, The derivatives include compounds HJW1107 and / or CZY1111, wherein the chemical structural formula of compound HJW1107 is shown in Formula II, and the chemical structural formula of compound CZY1111 is shown in Formula V. Formula II; Formula V.

3. The application as described in claim 1, characterized in that, The small RNA virus includes at least one of enterovirus D68, coxsackievirus A10, and encephalomyocarditis virus.

4. The application as described in claim 1, characterized in that, The drug is a drug that inhibits the infection and proliferation of small RNA viruses.

5. The application as described in claim 1, characterized in that, The drug also includes pharmaceutically acceptable excipients and carriers.

6. The application as described in claim 1, characterized in that, The drug is in the form of tablets, granules, pills, capsules, injections, or dispersants.

7. Use of salicylamide and / or its derivatives in the preparation of medicaments for the prevention and / or treatment of diseases caused by small RNA viruses.

8. The application as described in claim 7, characterized in that, The drug is for the prevention and / or treatment of respiratory diseases and / or acute flaccid myelitis caused by enterovirus D68.

9. The application as described in claim 7, characterized in that, The drug is for the prevention and / or treatment of hand, foot and mouth disease caused by Coxsackievirus A10.

10. The application as described in claim 7, characterized in that, The drug is for the prevention and / or treatment of myocarditis and / or encephalitis caused by encephalomyocarditis virus.

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