A naphthalenone compound, a preparation method and application thereof

Abstract

The application discloses a novel naphthalenone compound, a pharmaceutical composition and a preparation method and application thereof, and discloses a structural formula of the compound as shown in the following formula A. The compound A is obtained by specific culture and fermentation of Streptomyces gamaensis, obtaining a fermentation liquor containing the compound A, and then being separated and obtained from the fermentation liquor by a specific separation and purification method. The compound A has significant antiviral activity, especially shows excellent inhibition effect on tobacco mosaic virus (TMV), and the inhibition rate is as high as 79.21%, which is superior to existing commercial antiviral drugs ningnanmycin, provides an important candidate compound for development of a novel environment-friendly biological antiviral drug, and can be used for development of the novel environment-friendly biological antiviral drug.

Description

Technical Field

[0001] This invention belongs to the field of environmentally friendly biological pesticide technology, specifically relating to a novel naphthone compound with antiviral activity, its preparation method, and its application in the prevention and control of agricultural viral diseases. Background Technology

[0002] Plant viral diseases are a serious threat to agricultural production, often referred to as the "cancer" of plants. Tobacco Mosaic Virus (TMV), one of the most thoroughly studied plant viruses, can infect more than 200 plant species, including tobacco, tomato, and cucumber, causing enormous economic losses to global agriculture. However, due to the obligate parasitic nature, rapid replication, and diverse transmission routes of plant viruses, there are no absolutely effective control methods. Therefore, developing new and highly effective antiviral drugs is a major need in the agricultural field.

[0003] The research and development of antiviral pesticides in my country has long lagged behind that of pesticides for fungal and bacterial diseases. Currently, fewer than 20 antiviral pesticides with active ingredients are registered in my country. Chemical pesticides pose residue risks and are environmentally unfriendly. Biological pesticides, due to their environmentally friendly characteristics, are receiving increasing attention. Among existing antiviral biological pesticides, Ningnanmycin (Formula B) dominates the market, creating a "Ningnanmycin monopoly." CN93104287.9 ​​discloses that Ningnanmycin is a cytosine nucleoside peptide antibiotic produced by *Streptomyces noursei var. xichangensis*, and it has certain control effects against various plant viral diseases. However, long-term single-use of Ningnanmycin carries a significant risk of resistance development. Farmers lack effective alternatives, and if resistance to Ningnanmycin intensifies, they will face a "no pesticide available" dilemma. Therefore, developing antiviral biological pesticides with different structures and novel mechanisms of action to break the existing market pattern is of significant practical importance.

[0004]

[0005] Formula B

[0006] Microorganisms (such as Streptomyces) are an important source of naturally occurring bioactive compounds. However, discovering novel antiviral compounds from microorganisms faces numerous challenges: Firstly, microbial secondary metabolites are highly diverse, complex, and unknown, influenced by multiple variables such as strain type and culture conditions. Even the secondary metabolites produced by the same strain under different conditions can vary significantly, making the existence of novel, bioactive compounds highly uncertain. Secondly, microbial secondary metabolites are typically structurally complex, low in content, and diverse in composition, making the targeted isolation of target compounds technically difficult. The isolation process often yields known compounds or weakly active components. Naphthones are an important class of natural products with various biological activities, including anti-inflammatory and antitumor effects. However, current research on the antiviral activity of microbial naphthones against plant viruses, especially the isolation of naphthones with significant antiviral activity from Streptomyces, has not been reported.

[0007] In summary, how to isolate and obtain novel, environmentally friendly naphthone-based antiviral compounds with excellent activity from complex and unknown microbial secondary metabolites, so as to enrich the candidate compound library of antiviral drugs, solve the problem of viral diseases in agricultural production, and get rid of the dilemma of "no drugs available", is an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0008] To address the technical challenges of existing antiviral drugs, such as limited variety, high risk of drug resistance, difficulty in discovering antiviral compounds derived from microorganisms, and the need to reduce environmental pollution, this invention conducts in-depth research on the secondary metabolites of Streptomyces gamaensis. By optimizing fermentation culture conditions and establishing an efficient separation and purification process, a novel naphthone compound was successfully obtained. Furthermore, this compound was demonstrated to have excellent inhibitory activity against tobacco mosaic virus and is more environmentally friendly.

[0009] Based on this, in a first aspect, the present invention provides a naphthone-type compound of formula A with the structure shown below:

[0010]

[0011] Formula A.

[0012] The molecular formula of the compound described in this invention is C 14 H 16 O6, with a molecular weight of 280, is a white amorphous powder, readily soluble in methanol, ethanol, acetone, etc., but insoluble in water. This compound possesses a unique naphthone skeleton structure, with hydroxyl and carboxyl functional groups at specific positions, making it a novel secondary metabolite.

[0013] Secondly, the present invention provides a method for preparing the above-mentioned naphthone compound A, the method comprising:

[0014] Step 1, obtaining fermentation broth: Streptomyces gamaensis was cultured in seed culture medium and fermented in fermentation culture medium to prepare a fermentation broth containing compound A.

[0015] Step 2, extraction and purification: includes three steps: (a), (b), and (c).

[0016] Step (a) Pretreatment and resin treatment: The fermentation broth obtained in step one is centrifuged to obtain cell bodies and supernatant. The supernatant is then treated with macroporous adsorption resin, that is, the supernatant is adsorbed, eluted and concentrated by macroporous adsorption resin to obtain an oily substance.

[0017] Step (b) Silica gel column chromatography and gel column chromatography: The oily substance obtained in step (a) was subjected to silica gel column chromatography to obtain three components, namely component 1, component 2 and component 3, wherein the specific shift value (RF) of component 3 was 0.49 - 0.59; component 3 was subjected to gel column chromatography to obtain component 3-2.

[0018] Step (c) Reversed-phase preparative column chromatography: Component 3-2 obtained in step (b) was subjected to reversed-phase preparative column chromatography, and the product with a retention time of 23.0 min was collected to obtain compound A.

[0019] In a preferred embodiment, the fermentation medium in step one comprises: fructose 10-12 g / L, yeast powder 25-30 g / L, malt extract 25-30 g / L, CaCO3 0.3-0.4 g / L, pH 7.0-7.2, with the remainder being water; preferably, the fermentation medium comprises: fructose 10 g / L, yeast powder 25 g / L, malt extract 25 g / L, CaCO3 0.3 g / L, pH 7.0; the fermentation time is 8 days, and the temperature is 26-28℃.

[0020] In a preferred embodiment, the macroporous adsorption resin in step (a) is HPD-300 macroporous adsorption resin. This resin exhibits good adsorption selectivity for compound A and can effectively enrich the target compound.

[0021] In a preferred embodiment, the elution process of silica gel column chromatography in step (b) is a gradient elution at a volume ratio of petroleum ether:acetone = 100:0-50:50; the gel column in step (b) is a dextran gel G-25 column, and the eluent used for the gel column chromatography is methanol. By specifically optimizing the silica gel column chromatography and gel column chromatography conditions, this specific combination effectively removes impurities and enriches the target compound—compound A.

[0022] In a preferred embodiment, the chromatographic column used for reversed-phase preparative column chromatography in step (4) is an Agilent TC-C18 column with a particle size of 5 μm, a column length of 250 mm, and an inner diameter of 9.4 mm; the eluent used is a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water is 20:80. Reversed-phase preparative column chromatography is a key step in the separation and purification process of this invention. By optimizing chromatographic conditions and collecting components with specific retention times, high-purity compound A is obtained.

[0023] In a preferred embodiment, the seed culture medium comprises: 5-6 g / L glucose, 5-6 g / L soybean meal, 1.0-1.2 g / L malt extract, 5-6 g / L yeast extract, 1.0-1.2 g / L casein peptone, pH 7.0-7.2, with the remainder being water; the seed culture temperature is 25-28℃, and the time is 45-50 h, preferably 46 h.

[0024] In a preferred embodiment, prior to step one, a slant culture step is included, wherein the culture medium for the slant culture comprises: 10 g / L glucose, 3 g / L maltose, 3 g / L yeast extract, 0.5 g / L K2HPO4·3H2O, 0.5 g / L MgSO4·7H2O, 0.5 g / L NaCl, 1.0 g / L KNO3, 20 g / L agar powder, and pH 7.0.

[0025] Thirdly, the present invention also provides a pharmaceutical composition containing the compound of formula A according to claim 1, wherein the concentration of the compound of formula A in the pharmaceutical composition is 100-400 mg / L, preferably 200-400 mg / L, and more preferably 400 mg / L.

[0026] In a preferred embodiment, the pharmaceutical composition may further comprise conventional excipients acceptable in pesticides. These conventional excipients are those commonly used by those skilled in the art when preparing pesticide compositions. Examples of these conventional excipients include one or more of wetting agents, emulsifiers, dispersants, stabilizers, preservatives, synergists, and fillers. Preferably, they are one or more of wetting agents, dispersants, and fillers. More preferably, the wetting agent may be sodium dodecylbenzene sulfonate, etc., the filler may be kaolin, silica, diatomaceous earth, etc., and the dispersant may be sodium lignosulfonate.

[0027] The dosage form of the pharmaceutical composition of the present invention can be water-dispersible granules, emulsifiable concentrates, aqueous suspensions, oil suspensions, microemulsions, wettable powders, aqueous solutions, or tablets.

[0028] In a preferred embodiment, the pharmaceutical composition is a wettable powder containing compound A, sodium dodecyl sulfate, sodium lignosulfonate, silica, and kaolin; more preferably, the wettable powder comprises: 4% (by mass) compound A, 2% sodium dodecyl sulfate, 5% sodium lignosulfonate, 8% silica, and 81% kaolin; the wettable powder is diluted with water before use to make the concentration of compound A 200-400 mg / L.

[0029] Fourthly, this invention further provides the application of compound A and its pharmaceutical compositions in the preparation of antiviral drugs or antiviral pesticide compositions; preferably, the virus is a plant virus, more preferably tobacco mosaic virus, tomato yellow leaf curl virus, cucumber mosaic virus, or pepper mottle virus. Experimental results show that compound A has significant inhibitory activity against tobacco mosaic virus, with an inhibition rate as high as 79.21% at a concentration of 400 mg / L, and even at a concentration of 100 mg / L, the inhibition rate still reaches 66.26%, both superior to ningnanmycin at the same concentration (inhibition rate 64.35%), demonstrating excellent antiviral activity and good application prospects. Simultaneously, compositions containing compound A also exhibit significant inhibitory activity against tobacco mosaic virus.

[0030] The strain *Streptomyces gamaensis* used in this invention and embodiments is a *Streptomyces* strain isolated from soil. The 16S rRNA of this strain is registered in GenBank under the number KT963951. This strain was provided by the Biochemical Laboratory of Northeast Agricultural University and is deposited at the China General Microbiological Culture Collection Center (CGMCC) under accession number CGMCC No. 4.7304 (this strain has been published in the journal: Antonie Van Leeuwenhoek. 2017; 110 (4): 471-477. *Streptomyces gamaensis* sp.nov., a novel actinomycete with antifungal activity isolated from soil in Gama, Chad. Shanshan Zhao, Lan Ye, Chongxi Liu, AdamYacoub Abagana, Weiwei Zheng, Pengyu Sun, Jiansong Li, Wensheng Xiang, Xiangjing Wang).

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] 1. Through systematic optimization of fermentation conditions and study of secondary metabolites of Streptomyces gamaensis, this invention has for the first time isolated a novel naphthone compound from this strain and found that the compound has significant inhibitory activity against plant viruses (such as tobacco mosaic virus), providing an important candidate compound for the development of novel antiviral biopesticides.

[0033] 2. This invention establishes a complete process for the efficient separation and purification of compound A from the fermentation broth of Streptomyces gamaensis, including optimized fermentation conditions and the establishment of efficient separation and purification processes (optimization of conditions for macroporous resin adsorption, silica gel column chromatography, gel column chromatography, and reversed-phase preparative column chromatography, etc.), which can obtain high-purity compound A, laying the foundation for further research and large-scale application of this compound.

[0034] 3. The compound of formula A described in this invention is a natural product derived from microorganisms. It is environmentally friendly, low in toxicity, and low in residue, which is in line with the development direction of green pesticides. It can be further developed into a new type of environmentally friendly biological antiviral pesticide for the prevention and control of plant viral diseases such as tobacco mosaic virus.

[0035] 4. The discovery of compound A in this invention enriches the structural types of antiviral compounds derived from microorganisms, breaks the current situation of single antiviral biological pesticide varieties and similar mechanisms of action, provides a new option for solving the problem of drug resistance, and has important application value.

[0036] 5. The present invention develops a novel pharmaceutical composition containing compound A, which also exhibits significant inhibitory activity against plant viruses (e.g., tobacco compound viruses). Attached Figure Description

[0037] Figure 1 It is compound A obtained in Example 2. 1 H-NMR spectrum (MeOD).

[0038] Figure 2 It is compound A obtained in Example 2. 13 C10 NMR spectrum (MeOD).

[0039] Figure 3 This is the HSQC spectrum (MeOD) of compound A obtained in Example 2.

[0040] Figure 4 This is the HMBC spectrum (MeOD) of compound A obtained in Example 2.

[0041] Figure 5 It is compound A obtained in Example 2. 1 H- 1 H COSY spectrum (MeOD).

[0042] Figure 6 This is the NOESY spectrum (MeOD) of compound A obtained in Example 2.

[0043] Figure 7 This is the mass spectrum (ESI-MS) of compound A obtained in Example 2.

[0044] Figure 8 This is the infrared absorption spectrum (IR) (KBr) of compound A obtained in Example 2.

[0045] Figure 9 This is the ultraviolet absorption spectrum (UV) of compound A obtained in Example 2 (EtOH). Detailed Implementation

[0046] The present invention will be described in detail below with reference to the specific embodiments described. It must be noted that these embodiments are for illustrative purposes only and are not intended to limit the invention. The following descriptions are merely preferred embodiments of the invention, and the invention is not limited to the specific implementations described below. Any modifications, equivalent substitutions, or improvements within the technical scope disclosed in the invention should be included within the protection scope of the invention. In the following embodiments, unless otherwise specified, all temperatures are in Celsius. Unless otherwise specified, all raw materials and reagents are commercially available and used directly without further purification. Unless otherwise specified, the experimental methods described in this invention are conventional methods.

[0047] Example 1 Fermentation

[0048] Step ① Slant culture: Inoculate Streptomyces gamaensis into slant culture medium. The formula of the slant culture medium (g / L) is as follows: glucose 10, maltose 3, yeast extract 3, K2HPO4·3H2O 0.5, MgSO4·7H2O 0.5, NaCl 0.5, KNO3 1.0, agar powder 20, pH 7.0, and the remainder is water. Incubate at 28℃ for 8 days.

[0049] Step ② Seed culture: Add 10 ml of water to the slant culture medium containing the inoculum, and scrape off the spores with a sterilized inoculation loop to prepare a 10% concentration. 7 CFU ml -1 Spore suspension. Take 2 ml of the spore suspension and inoculate it into a 250 ml shake flask containing seed culture medium, resulting in a total volume of 25 ml. Incubate on a rotary shaker at 250 rpm and 28°C for 46 hours to obtain the seed culture. The seed culture medium formula (g / L) is: glucose 5, soybean meal 5, malt extract 1.0, yeast extract 5, casein peptone 1.0, pH 7.0, with the remainder being water. Sterilize at 121°C for 20 minutes.

[0050] Step ③ Fermentation: Inoculate the seed culture at an 8% (V / V) inoculation rate into a 1 L fermentation shaker flask, filling the flask to a volume of 100 ml. Incubate at 250 rpm and 28 ℃ on a rotary shaker for 8 days to obtain a fermentation broth containing compound A. The fermentation medium formula (g / L) is: fructose 10, yeast powder 25, malt extract 25, CaCO3 0.3, pH 7.0, with the remainder being water. Sterilize at 121 ℃ for 20 minutes.

[0051] Example 2: Extraction, Separation, and Structural Identification

[0052] (1) Extraction and separation

[0053] Step (a) Pretreatment and resin treatment: 30 L of fermentation broth prepared in Example 1 was centrifuged to separate the solid and liquid components, and the cells and supernatant were collected separately. The supernatant was loaded onto HPD-300 macroporous resin for adsorption. After rinsing the resin with water, elution was performed with 90% ethanol, and the eluent was collected. The ethanol eluent was concentrated under reduced pressure at 45 °C, the ethanol solvent was evaporated, and the solution was concentrated to dryness, finally yielding 20 g of oily substance.

[0054] Step (b) Silica gel column chromatography and gel column chromatography: The oily substance prepared in step (a) was loaded onto a silica gel column with a particle size of 100-200 mesh for chromatographic separation. Gradient elution was performed using a petroleum ether-acetone solution with a volume ratio of 100:0 to 50:50, and the elution flow rate was controlled at 30 ml / min. The eluent was collected fractionally in 250 ml Erlenmeyer flasks, with each fraction having a volume of 250 ml. Thin-layer chromatography (TLC) was performed using petroleum ether:acetone = 2:1 as the developing solvent. The same components were combined to obtain fraction 1 with a specific gravity (RF) of 0.70-0.80, fraction 2 with a RF of 0.60-0.69, and fraction 3 with a RF of 0.49-0.59. Fraction 3 was separated into fractions 3-2 by dextran gel G-25 column chromatography with methanol as the elution solvent.

[0055] Step (c) Reversed-phase preparative column chromatography: Component 3-2 obtained in step (b) was subjected to reversed-phase preparative column chromatography. The peak with a retention time of 23.0 min was collected to obtain compound A, under the following conditions:

[0056] Instrument: Agilent 1260 semi-preparative high-performance liquid chromatograph;

[0057] The chromatographic column was an Agilent TC-C18 column (5 μm, 250 × 9.4 mm);

[0058] Eluent: Acetonitrile / water = 20 / 80 (V / V); Flow rate: 1.5 mL / min;

[0059] Detection wavelength: λ=220 nm.

[0060] (2) Structural identification

[0061] The obtained compound A was subjected to structural identification, including but not limited to determining its solubility, specific rotation, mass spectrometry, ultraviolet light, infrared spectroscopy, and so on. 1 Multiple experiments, including H and 13C NMR (CDCl3), yielded the following results: Compound A has the molecular formula C 14 H 16 O6, a white amorphous powder; readily soluble in methanol, ethanol, and acetone, but insoluble in water;

[0062]

[0063] Compound I 1 H and 13 The C NMR (CDCl3) data are shown in Table 1.

[0064] Table 1. Compound A 1 H and 13 C NMR (CDCl3) data

[0065]

[0066] Based on the above data, the structural formula of compound A is determined as follows:

[0067]

[0068] Formula A

[0069] Example 3: Antiviral activity assay

[0070] The inhibitory activity of compound A against tobacco mosaic virus (TMV) was determined using the half-leaf necrotic spot method. Four- to six-leaf stage Nicotiana glutinosa was selected as the host for TMV necrotic spots, and whole leaves were inoculated using the conventional sap rubbing method. Two days after inoculation, the Nicotiana glutinosa was sprayed with compound A solution (the control group underwent the same treatment). Fourteen days later, disease incidence was observed, the number of necrotic spots was recorded, and the disease index and inhibition rate were calculated. Ningnanmycin (2% aqueous solution) was used as a positive control, and water as a blank control. Each experiment was performed in triplicate, and the average value was taken. The experimental results are shown in Table 2.

[0071] The formulas for calculating the disease index and inhibition rate are as follows:

[0072] Disease index = ∑(Number of diseased leaves at each level × Relative grade value) / (Total number of leaves surveyed × Highest grade value) × 100%

[0073] Inhibition rate = (Control disease index - Treatment disease index) / Control disease index × 100%

[0074] Table 2. Inhibitory effect of compound A on tobacco mosaic virus (TMV)

[0075]

[0076] As shown in Table 2, compound A exhibits significant inhibitory activity against tobacco mosaic virus at concentrations of 100-400 mg / L. At a concentration of 400 mg / L, compound A showed an inhibition rate of 79.21% against tobacco mosaic virus; at a concentration of 100 mg / L, the inhibition rate still reached 66.26%, higher than the antiviral activity of ningnanmycin at the same concentration (64.35%). This indicates that compound A still exhibits strong inhibitory activity against tobacco mosaic virus even at lower concentrations, and its activity is superior to that of the existing commercially available antiviral drug ningnanmycin, demonstrating good prospects for development and application.

[0077] Example 4 Preparation of the pharmaceutical composition

[0078] Take 4g of compound A, add 2g of sodium dodecyl sulfate, 5g of sodium lignosulfonate, 8g of silica, and kaolin to a final volume of 100g. Mix thoroughly and then air-jet pulverize to obtain a wettable powder (containing 4% compound A). This wettable powder is diluted with water to achieve a compound A concentration of 200-400 mg / L. For example, take 5.0g and 10.0g of the 4% compound A wettable powder, add 1L of water, stir to fully wet and disperse, and prepare solutions with compound A concentrations of 200 and 400 mg / L (the solution with a compound A concentration of 200 mg / L is designated as solution 1, and the solution with a compound A concentration of 400 mg / L is designated as solution 2). These solutions can be directly used for spraying to control plant viruses, such as tobacco mosaic virus.

[0079] Example 5 Inhibitory activity against tobacco mosaic virus

[0080] Using the same method as in Example 3, the inhibitory activity of drug solution 1 (compound A concentration of 200 mg / L) and drug solution 2 (compound A concentration of 400 mg / L) against tobacco mosaic virus (TMV) was determined. The following results were obtained: the inhibition rate of drug solution 1 was 70.51%; the inhibition rate of drug solution 2 was 79.17%. The results indicate that both drug solutions 1 and 2 have good inhibitory effects on tobacco mosaic virus.

Claims

1. A naphthone-type compound of formula A with the structure shown below: Formula A.

2. A method for preparing compound A according to claim 1, characterized in that, The preparation method includes: Step 1, obtaining fermentation broth: Streptomyces gamaensis was cultured in seed culture medium and fermented in fermentation culture medium to prepare a fermentation broth containing compound A. Step 2, Extraction and Separation: This includes three steps: (a), (b), and (c). Step (a) Pretreatment and resin treatment: The fermentation broth obtained in step one is centrifuged to obtain cell bodies and supernatant. The supernatant is then treated with macroporous adsorption resin, that is, the supernatant is adsorbed, eluted and concentrated by macroporous adsorption resin to obtain an oily substance. Step (b) Silica gel column chromatography and gel column chromatography: The oily substance obtained in step (a) was subjected to silica gel column chromatography to obtain three components, namely component 1, component 2 and component 3, wherein the specific shift value (RF) of component 3 was 0.49 - 0.59; component 3 was subjected to gel column chromatography to obtain component 3-2. Step (c) Reversed-phase preparative column chromatography: Component 3-2 obtained in step (b) was subjected to reversed-phase preparative column chromatography, and the product with a retention time of 23.0 min was collected to obtain compound A.

3. The preparation method according to claim 2, characterized in that: The fermentation medium in step one comprises: fructose 10-12 g / L, yeast powder 25-30 g / L, malt extract 25-30 g / L, CaCO3 0.3-0.4 g / L, pH 7.0-7.2, with the remainder being water; preferably, the fermentation medium comprises: fructose 10 g / L, yeast powder 25 g / L, malt extract 25 g / L, CaCO3 0.3 g / L, pH 7.0; the fermentation time is 8 days, and the temperature is 26-28℃.

4. The method according to claim 2, characterized in that: The macroporous adsorption resin in step (a) is HPD-300 macroporous adsorption resin.

5. The method according to claim 2, characterized in that: The elution process of the silica gel column chromatography in step (b) is a gradient elution at a volume ratio of petroleum ether:acetone = 100:0-50:50; the gel column in step (b) is a dextran gel G-25 column, and the eluent used for the gel column chromatography is methanol.

6. The method according to claim 2, characterized in that: The chromatographic column used in the reversed-phase preparative column chromatography in step (4) is an Agilent TC-C18 column with a particle size of 5 μm, a column length of 250 mm, and an inner diameter of 9.4 mm. The eluent used is a mixed solvent of acetonitrile and water, wherein the volume ratio of acetonitrile to water is 20:

80.

7. The method according to claim 2, characterized in that, The seed culture medium comprises: 5-6 g / L glucose, 5-6 g / L soybean meal, 1.0-1.2 g / L malt extract, 5-6 g / L yeast extract, 1.0-1.2 g / L casein peptone, pH 7.0-7.2, with the remainder being water; the seed culture temperature is 25-28℃, and the time is 45-50 h, preferably 46 h.

8. A pharmaceutical composition comprising the compound of formula A according to claim 1, wherein the concentration of the compound of formula A in the pharmaceutical composition is 100-400 mg / L, preferably 200-400 mg / L, and more preferably 400 mg / L.

9. The pharmaceutical composition of claim 8 may further comprise conventional pesticide excipients; preferably, the pharmaceutical composition is a wettable powder containing compound A, sodium dodecyl sulfate, sodium lignosulfonate, silica, and kaolin; more preferably, the wettable powder comprises: 4% compound A, 2% sodium dodecyl sulfate, 5% sodium lignosulfonate, 8% silica, and 81% kaolin; the wettable powder is diluted with water before use to make the concentration of compound A 200-400 mg / L.

10. The use of a compound of formula A as described in claim 1, or a pharmaceutical composition as described in claim 8 or 9, in the preparation of an antiviral drug or an antiviral pesticide composition, preferably, the virus is a plant virus, more preferably tobacco mosaic virus, tomato yellow leaf curl virus, cucumber mosaic virus, or pepper mottle virus.

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