A compound for use in the treatment of fever and thrombocytopenia syndrome and its use

Abstract

The application discloses a compound or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer, a prodrug molecule, a metabolite thereof for fever with thrombocytopenia syndrome. The application has carried out in-depth research on active ingredients of Plumbago zeylanica L., successfully found a key site with anti-SFTSV activity, and further screened a compound with an anti-SFTSV effect. The research finding provides a scientific basis for developing a specific treatment drug for SFTS.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical technology, and in particular to a compound for fever with thrombocytopenia syndrome and its application. Background Technology

[0002] Severe Fever with Thrombocytopenia Syndrome (SFTS), commonly known as tick-borne disease, is an acute infectious disease caused by a newly discovered Dabie bandavirus (SFTSV) belonging to the order Bunyavirales. Clinical manifestations of SFTS include fever, thrombocytopenia, leukopenia, gastrointestinal symptoms, and multiple organ dysfunction, with an initial mortality rate of approximately 30%. The incubation period is 7-14 days, and the course of the disease consists of three phases: the febrile phase, the multiple organ failure phase, and the recovery phase. SFTSV is primarily transmitted through tick bites, with the Asian longhorned tick (Haemaphysalis longicornis) as the main vector. The virus has also been detected in the American tick (Amblyomma testudinarium) and the hard tick (Ixodes nipponensis). Furthermore, close contact with infected animals (such as cats and dogs) or direct contact with the bodily fluids of infected individuals (such as blood and sputum) can lead to human-to-human transmission. SFTSV poses a significant public health threat in China and other parts of Asia and has been listed by the World Health Organization as a pathogen of urgent concern.

[0003] The natural transmission cycle of SFTSV is not fully understood. Ticks are the primary vector, and humans are occasional hosts. As human activities (such as agriculture and outdoor work) encroach on natural habitats, the risk of exposure to tick-borne pathogens increases, leading to viral spillover from natural foci. Recently, the scope of SFTS outbreaks in Asia has expanded, with the vector spreading across regions, indicating an increased risk of epidemics and pandemics, and the potential for hospital-acquired transmission. Currently, SFTS diagnosis mainly relies on reverse transcription polymerase chain reaction (RT-PCR) to detect viral RNA, but this method is time-consuming and requires sophisticated equipment, limiting its clinical application. Treatment primarily involves supportive care (such as fluid replacement, electrolyte balance, and plasma and platelet transfusions), but the effectiveness is limited.

[0004] Natural products, due to their structural diversity and bioactivity, have become an important source for developing anti-SFTSV therapies. Justicia procumbens, a traditional herb, possesses various pharmacological activities. This study aims to discover lead compounds with anti-SFTSV activity through systematic screening and optimization of Justicia procumbens extract, providing a scientific basis for developing specific therapeutic drugs against SFTS. Summary of the Invention

[0005] The present invention aims to conduct a more in-depth study on the active ingredients of Acanthopanax and to discover its active ingredients against SFTSV.

[0006] In view of this, the first aspect of the present invention provides a compound or its pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, or metabolite for fever with thrombocytopenia syndrome, wherein the compound is selected from:

[0007]

[0008] Preferably, the compound is selected from C2 or C5.

[0009] A second aspect of the present invention provides the use of the compound as described above, or its pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, or metabolite, for the preparation of a composition for use in fever with thrombocytopenia syndrome.

[0010] Preferably, the treatment for fever with thrombocytopenia syndrome includes one or more of the following: (i) relieving high fever, thrombocytopenia, leukopenia and gastrointestinal symptoms; (ii) suppressing neurological symptoms, bleeding in multiple organ dysfunction and multiple organ injury; (iii) promoting hematopoietic function and immune system reconstruction; (iv) anti-SFTSV infection.

[0011] Preferably, the composition is a pharmaceutical composition.

[0012] Preferably, the composition further includes a pharmaceutically acceptable carrier.

[0013] Preferably, the dosage form of the composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

[0014] Preferably, the dosage form of the composition is an oral preparation, a topical preparation, or an injectable preparation.

[0015] Preferably, the dosage form of the composition is tablets, capsules, soft capsules, gels, oral preparations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, lyophilized injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations, or controlled-release preparations.

[0016] Preferably, the injectable preparation is an intravenous injection preparation, an intramuscular injection preparation, a subcutaneous injection preparation, an intradermal injection preparation, or an intraperitoneal injection preparation.

[0017] Preferably, the composition is administered to humans or non-human mammals.

[0018] Preferably, the object is a human or a non-human mammal.

[0019] Preferably, the non-human mammal is a mouse, rat, rabbit, cow, sheep, dog, or horse.

[0020] A third aspect of the present invention provides an active fraction for fever with thrombocytopenia syndrome, characterized in that the active fraction is selected from: n-butanol extract or ethyl acetate extract; wherein the preparation method of the ethanol extract includes: taking Acanthopanax papyriferus herb, mixing it with 60% ethanol aqueous solution, reflux extraction at 90°C for 2 hours, and repeating the extraction 3 times; combining the three extracts, concentrating under reduced pressure until there is no alcohol odor, to obtain a dark brown paste-like crude extract.

[0021] A fourth aspect of the present invention provides the use of the active site as described above for preparing a composition for use in fever with thrombocytopenia syndrome.

[0022] Preferably, the treatment for fever with thrombocytopenia syndrome includes one or more of the following: (i) relieving high fever, thrombocytopenia and gastrointestinal symptoms; (ii) inhibiting central nervous system symptoms, bleeding and multiple organ damage; (iii) promoting hematopoietic function and immune system reconstruction; and (iv) combating SFTSV infection.

[0023] Preferably, the composition is a pharmaceutical composition.

[0024] Preferably, the composition further includes a pharmaceutically acceptable carrier.

[0025] Preferably, the dosage form of the composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

[0026] Preferably, the dosage form of the composition is an oral preparation, a topical preparation, or an injectable preparation.

[0027] Preferably, the dosage form of the composition is tablets, capsules, soft capsules, gels, oral preparations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, lyophilized injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations, or controlled-release preparations.

[0028] Preferably, the injectable preparation is an intravenous injection preparation, an intramuscular injection preparation, a subcutaneous injection preparation, an intradermal injection preparation, or an intraperitoneal injection preparation.

[0029] Preferably, the composition is administered to humans or non-human mammals.

[0030] Preferably, the object is a human or a non-human mammal.

[0031] Preferably, the non-human mammal is a mouse, rat, rabbit, cow, sheep, dog, or horse.

[0032] A fifth aspect of the present invention provides a pharmaceutical composition comprising the active site as described above.

[0033] Preferably, the composition further includes a pharmaceutically acceptable carrier.

[0034] Preferably, the dosage form of the composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

[0035] Preferably, the dosage form of the composition is an oral preparation, a topical preparation, or an injectable preparation.

[0036] Preferably, the dosage form of the composition is tablets, capsules, soft capsules, gels, oral preparations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, lyophilized injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations, or controlled-release preparations.

[0037] Preferably, the injectable preparation is an intravenous injection preparation, an intramuscular injection preparation, a subcutaneous injection preparation, an intradermal injection preparation, or an intraperitoneal injection preparation.

[0038] Preferably, the composition is administered to humans or non-human mammals.

[0039] Preferably, the object is a human or a non-human mammal.

[0040] Preferably, the non-human mammal is a mouse, rat, rabbit, cow, sheep, dog, or horse.

[0041] The sixth aspect of the present invention provides a method for preventing and / or treating fever with thrombocytopenia syndrome, the method comprising administering to a desired subject a compound as described in the first aspect of the present invention or a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, metabolite thereof, a composition as described in the second aspect of the present invention, an active site as described in the third aspect of the present invention, or a composition as described in the fifth aspect of the present invention.

[0042] Preferably, the treatment for fever with thrombocytopenia syndrome includes one or more of the following: (i) relieving high fever, thrombocytopenia, leukopenia and gastrointestinal symptoms; (ii) suppressing neurological symptoms, bleeding in multiple organ dysfunction and multiple organ injury; (iii) promoting hematopoietic function and immune system reconstruction; (iv) anti-SFTSV infection.

[0043] Preferably, the compound or its pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, metabolite, active site, or combination thereof can be administered in multiple doses.

[0044] Preferably, the object is a human or a non-human mammal.

[0045] Preferably, the non-human mammal is a mouse, rat, rabbit, cow, sheep, dog, or horse.

[0046] Preferably, the administration includes oral administration or injection.

[0047] Preferably, the injection administration is intravenous injection, intramuscular injection, subcutaneous injection, intradermal injection, or intraperitoneal injection.

[0048] The seventh aspect of the present invention provides the use of the compound as described above or its pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, metabolite; or the aforementioned active site for the preparation of a composition for use against severe febrile hemophagocytic virus.

[0049] Preferably, the anti-severe febrile hemophagocytic virus comprises one or more selected from the group consisting of: (i) reducing the viral load of SFTSV; and (ii) inhibiting the replication or spread of SFTSV.

[0050] Preferably, the composition is a pharmaceutical composition.

[0051] Preferably, the composition further includes a pharmaceutically acceptable carrier.

[0052] Preferably, the dosage form of the composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

[0053] Preferably, the dosage form of the composition is an oral preparation, a topical preparation, or an injectable preparation.

[0054] Preferably, the dosage form of the composition is tablets, capsules, soft capsules, gels, oral preparations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, lyophilized injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations, or controlled-release preparations.

[0055] Preferably, the injectable preparation is an intravenous injection preparation, an intramuscular injection preparation, a subcutaneous injection preparation, an intradermal injection preparation, or an intraperitoneal injection preparation.

[0056] Preferably, the composition is administered to humans or non-human mammals.

[0057] Preferably, the object is a human or a non-human mammal.

[0058] Preferably, the non-human mammal is a mouse, rat, rabbit, cow, sheep, dog, or horse.

[0059] This invention conducted an in-depth study of the active components of *Acanthopanax*, successfully identifying key sites possessing anti-SFTSV activity. Based on this, this study used Huh7 cells as a model and employed qRT-PCR to detect the RNA level of SFTSV in the cell culture supernatant after SFTSV infection, thereby assessing the inhibitory effect of lignans in *Acanthopanax* on SFTSV infection. Through this process, compounds with anti-SFTSV activity were further screened. This study discovered lead compounds with anti-SFTSV activity, providing a scientific basis for the development of specific therapeutic drugs against SFTS. Attached Figure Description

[0060] Figure 1 The morphological changes of Huh7 cells after treatment with the compound of this invention are shown. Detailed Implementation

[0061] Severe fever with thrombocytopenia syndrome (SFTSV) is an immunopathological storm and coagulation collapse resulting from viral infection. Current treatments generally struggle to balance antiviral therapy with immunomodulation (e.g., hormones may suppress inflammation but exacerbate the infection). Its unique biological characteristics and disease mechanisms mean that it does not show significant antiviral activity against common antiviral drugs, and there are currently no specific drugs. For example, although ribavirin has broad-spectrum antiviral activity and has been used to treat various viral infections, it has not shown clinical benefit against SFTSV. Compared with the group not receiving ribavirin treatment, it neither increases platelet count nor reduces viral load (Lu et al., Case fatality and effectiveness of ribavirin in hospitalized patients with severe fever with thrombocytopenia syndrome in China). Previous studies have also shown that most antiviral active products are completely ineffective against SFTSV. Therefore, this invention aims to conduct further in-depth research on natural products to screen for highly effective and low-toxicity anti-SFTSV active ingredients and specific compounds. The following will describe this in detail with experimental examples.

[0062] It is particularly important to note that similar substitutions and modifications made to this invention are obvious to those skilled in the art, and they are all considered to be included in this invention. Those skilled in the art will clearly be able to modify or appropriately change and combine the methods and applications described herein without departing from the content, spirit, and scope of this invention to implement and apply the technology of this invention. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments.

[0063] Unless otherwise specified, this invention is carried out under conventional conditions or conditions recommended by the manufacturer. The raw materials or excipients used, as well as the reagents or instruments used, whose manufacturers are not specified, are all conventional products that can be obtained commercially.

[0064] Example 1: Preparation of the extract of the present invention

[0065] 50 kg of whole Justicia procumbens herbal material, dried at room temperature by forced air, was pulverized to an appropriate particle size using a pulverizer. A 60% ethanol aqueous solution (v / v) was used as the extraction solvent, and hot reflux extraction was performed at a material-to-liquid ratio of 1:8 (w / v). The specific process is as follows: The herbal powder was mixed with a 60% ethanol aqueous solution and refluxed at 90℃ for 2 hours, repeated three times. The three extracts were combined and concentrated under reduced pressure using a rotary evaporator until no alcohol odor remained, yielding a dark brown paste-like crude extract.

[0066] The crude extract was dispersed in water (solid-to-liquid ratio 1:20, w / v) and subjected to gradient extraction using a liquid-liquid extraction method. Petroleum ether (PE, boiling point 60-90℃), ethyl acetate (EtOAc), and n-butanol (n-Butanol, n-BuOH) were used successively as extraction solvents, with each solvent used in a volume three times that of the aqueous phase, and each solvent was used for extraction three times. The solvent extraction layers were collected separately and concentrated under reduced pressure to obtain the following extracts: ethyl acetate extract: 365 g, yield 9.1% (w / w); n-butanol extract: 405 g, yield 10.1% (w / w); aqueous layer residue.

[0067] Example 2: Preparation of the compounds of the present invention (B1-B6, C1-C8)

[0068]

[0069] The ethyl acetate extract of *Acanthopanax* was separated by normal-phase silica gel column chromatography (200-300 mesh). First, a gradient elution was performed with petroleum ether-acetone (100:0→0:100, v / v), followed by a gradient elution of the remaining highly polar residue with dichloromethane-methanol (100:0→0:100, v / v). Thin-layer chromatography (TLC) was used to analyze and combine similar fractions, ultimately yielding eight fractions EA-A to EA-H. Fractions EA-E were separated by silica gel column chromatography (petroleum ether-ethyl acetate, 100:0→0:100, v / v), and the 10th fraction was recrystallized in trichloromethane to give compound B3. Fractions EA-F were separated by silica gel column chromatography (chloroform-methanol, 100:0→0:100, v / v), and the 11th fraction was recrystallized in trichloromethane to give compound B4. Fractions EA-G were separated by silica gel column chromatography (petroleum ether-ethyl acetate, 100:0→0:100, v / v). Fractions 10-11 were combined and eluted with Sephadex LH-20 (chloroform-methanol = 1:1), and recrystallized in chloroform to give compound C2. Fractions EA-H were separated by silica gel column chromatography (chloroform-methanol, 100:0→0:100, v / v). Fractions 3-5 were recrystallized in chloroform to give compound B2, and fractions 7-8 were recrystallized in chloroform to give compound B1. Fractions EA-J were eluted by silica gel column chromatography with a petroleum ether-acetone gradient. The fourth fraction was eluted with methanol using Sephadex LH-20 and recrystallized to give compound B5. The sixth fraction was first separated by silica gel column chromatography (cyclohexane-ethyl acetate, 100:0 → 0:100, v / v) and then eluted sequentially with Sephadex LH-20 (chloroform-methanol = 1:1, methanol) to give compound C6. Fractions 8 and 9 were repeatedly eluted with Sephadex LH-20 (chloroform-methanol, 1:1 and methanol) to give compounds C3 and C1, respectively. Fraction 12 was eluted sequentially with Sephadex LH-20 (chloroform-methanol, 1:1 and methanol) and recrystallized in methanol to give compound C5. Fraction 14 was eluted with methanol using Sephadex LH-20 and recrystallized to give compound C4.

[0070] The n-butanol extract was subjected to AB-8 macroporous adsorption resin column chromatography with an ethanol-water gradient elution (0%, 25%, 50%, 95%, v / v), each elution volume being 3-5 times the resin volume. After concentration under reduced pressure, 25%, 50%, and 95% ethanol eluates were obtained. The 50% ethanol eluate (100 g) was selected for further separation. Silica gel column chromatography (200-300 mesh) was used with a dichloromethane-methanol gradient elution (100:0 → 0:100, v / v). TLC analysis of similar fractions yielded 11 fractions, nBu-A to nBu-K. Fraction nBu-D was further analyzed by silica gel column chromatography (chloroform-methanol, 100:0 → 0:100, v / v). Fractions 11-13 were eluted with Sephadex LH-20 methanol to obtain compound B6.

[0071] Compound structure identification data

[0072] Compound B1: JusticidinC

[0073] White powder, soluble in chloroform, ESI-MS m / z: 395 [M+H] + The molecular formula is C 22 H 18 O7. 1 H-NMR (400MHz, CDCl3)δ H : 6.82 (1H, d, J = 1.6Hz, H-2′), 6.97 (1H, d, J = 8.0Hz, H-5′), 6.80 (1H, dd, J = 1.6, 8.0Hz, H-6′), 6.99 (1H, s, H-5), 7.70 (1H, s, H-8), 5.14 (2 H, s, H-12), 4.38 (3H, s, 1-OCH3), 3.85 (3H, s, 6-OCH3), 4.07 (3H, s, 7-OCH3), 6.07 (1H, d, J = 1.2Hz, Ha-7′), 6.11 (1H, d, J = 1.2Hz, Hb-7′). 13 C-NMR (100MHz, CDCl3)δ C:155.4(C-1), 109.7(C-2), 139.0(C-3), 126.4(C-4), 104.1(C-5), 149.7(C- 6), 152.3(C-7), 102.2(C-8), 133.4(C-9), 123.6(C-10), 169.3(C-11), 68.8( C-12), 129.6(C-1′), 109.4(C-2′), 147.4(C-3′), 148.2(C-4′), 109.0(C-5′ ), 122.9(C-6′), 63.1(1-OCH3), 55.9(6-OCH3), 56.1(7-OCH3), 101.4(C-7′).

[0074] Compound B2: JusticidinD

[0075] White powder, slightly soluble in chloroform, ESI-MS m / z: 379 [M+H] + The molecular formula is C 21 H 14 O7. 1 H-NMR (400MHz, DMSO-d6)δ H : 7.00 (1H, d, J = 2.0Hz, H-2′), 7.08 (1H, d, J = 8.0Hz, H-5′), 6.86 (1H, dd, J = 2.0, 8.0Hz, H-6′), 6.93 (1H, s, H-5), 7.65 (1H, s, H-8), 5 .19 (1H, d, J=14.8Hz, Ha-12), 5.23 (1H, d, J=14.8Hz, Hb-12), 4.18 (3H, s, 1-OCH3), 6.13 (2H, s, H-7′), 6.21 (2H, d, J=2.0Hz, H-8′). 13 C-NMR (100MHz, DMSO-d6)δ C :154.5(C-1), 110.2(C-2), 139.8(C-3), 126.9(C-4), 101.2(C-5), 148. 1(C-6), 150.7(C-7), 99.3(C-8), 134.4(C-9), 124.4(C-10), 168.3(C-11 ), 68.5(C-12), 128.8(C-1′), 109.8(C-2′), 147.1(C-3′), 147.7(C-4′), 108.8(C-5′), 123.0(C-6′), 101.3(C-7′), 102.3(C-8′), 63.1(1-OCH3).

[0076] Compound B3: JusticidinE

[0077] White powder, soluble in chloroform, ESI-MS m / z: 349 [M+H] + The molecular formula is C 20 H 12 O6. 1 H-NMR (400MHz, CDCl3)δ H : 8.27 (1H, s, H-1), 7.10 (1H, s, H-5), 7.31 (1H, s, H-8), 5.18 (1H, d, J = 15.1Hz, Ha-12), 5.23 (1H, d, J = 15.1Hz, Hb-12) , 6.81 (1H, d, J = 1.7Hz, H-2′), 6.98 (1H, d, J = 8.0Hz, H-5′), 6.80 (1H, dd, J = 1.7, 8.0Hz, H-6′), 6.09 (4H, m, H-7′, 8′). 13 C-NMR (100MHz, CDCl3)δ C : 124.7(C-1), 138.4(C-2), 121.7(C-3), 131.3(C-4), 101.5(C-5), 148.4(C-6), 150.5(C-7), 105.3(C-8), 132.7(C-9), 133.4(C-10), 171 .4(C-11), 69.4(C-12), 129.6(C-1′), 109.7(C-2′), 148.3(C-3′), 14 7.7(C-4′), 109.0(C-5′), 122.7(C-6′), 101.9(C-7′), 102.0(C-8′).

[0078] Compound B4: 5′-Methoxyretrochinensin

[0079] White powder, soluble in chloroform, ESI-MS m / z: 395 [M+H] + The molecular formula is C 22 H 18 O7. 1 H-NMR (400MHz, CDCl3)δ H : 8.29 (1H, s, H-1), 7.11 (1H, s, H-5), 7.33 (1H, s, H-8), 6.54 (2H, s, H-2′, 6′), 5.23 (2H, s, H-12), 6.11 (2H, s, H-7′), 3.96 (3H, s, 4′-OCH3), 3.86 (6H, s, 3′, 5′-OCH3). 13C-NMR (100MHz, CDCl3)δ C : 171.4, 153.8, 150.6, 148.5, 138.2, 138.0, 133.2, 133.1, 131.6, 131.3, 124.8, 121.7, 106.3, 105.3, 102.1, 101.9, 69.4, 61.0, 56.3.

[0080] Compound B5: Detetrahydroconidendrin

[0081] Colorless crystals (MeOH), readily soluble in methanol, ESI-MS m / z: 353 [M+H] + The molecular formula is C 20 H 16 O6. 1 H-NMR (400MHz, CD3OD)δ H : 8.28(1H,s,H-1), 7.15(1H,s,H-5), 7.49(1H,s,H-8), 5.28(1H,s,Ha-12), 5.29(1H,s,Hb-12), 6.96(1H,s, H-2'), 6.99 (1H, d, J=8.4Hz, H-5'), 6.84 (1H, d, J=8.4Hz, H-6'), 4.02 (3H, s, 7-OCH3), 3.86 (3H, s, 3'-OCH3). 13 C-NMR (100MHz, CD3OD)δ C :124.9(C-1), 139.0(C-2), 121.4(C-3), 131.1(C-4), 109.0(C-5), 15 1.0(C-6), 151.3(C-7), 108.9(C-8), 133.3(C-9), 133.8(C-10), 174.4 (C-11), 71.2(C-12), 129.0(C-1′), 116.7(C-2′), 149.4(C-3′), 147.8(C-4′), 114.0(C-5′), 123.4(C-6′), 56.4(7-OCH3), 56.5(3′-OCH3).

[0082] Compound B6: Justicidinoside A

[0083] Colorless crystals (MeOH), readily soluble in methanol, ESI-MS m / z: 353 [M+H] + The molecular formula is C 28 H 28 O 13 . 1H-NMR (400MHz, CD3OD)δ H : 8.28(1H,s,H-1), 7.15(1H,s,H-5), 7.49(1H,s,H-8), 5.28(1H,s,Ha-12), 5.29(1H,s,Hb-12), 6.96(1H,s, H-2'), 6.99 (1H, d, J=8.4Hz, H-5'), 6.84 (1H, d, J=8.4Hz, H-6'), 4.02 (3H, s, 7-OCH3), 3.86 (3H, s, 3'-OCH3). 13 C-NMR (100MHz, CD3OD)δ C :124.9(C-1), 139.0(C-2), 121.4(C-3), 131.1(C-4), 109.0(C-5), 15 1.0(C-6), 151.3(C-7), 108.9(C-8), 133.3(C-9), 133.8(C-10), 174.4 (C-11), 71.2(C-12), 129.0(C-1′), 116.7(C-2′), 149.4(C-3′), 147.8(C-4′), 114.0(C-5′), 123.4(C-6′), 56.4(7-OCH3), 56.5(3′-OCH3).

[0084] Compound C1: Juspurpudin

[0085] Yellow amorphous powder, soluble in methanol, HR-ESI-MS m / z: 407.0516 [M+K] + The molecular formula is C 20 H 16 O7. 1 H-NMR (400MHz, CD3OD)δ H : 6.73 (2H, d, J = 8.1Hz, H-5′), 6.62 (2H, d, J = 1.7Hz, H-2′), 6.57 (2H, d, J = 8.1, 1.7Hz, H- 6′), 5.90(4H,s,3′-OCH2-4′), 5.14(1H,s,H-3a), 4.92(2H,s,H-5), 4.08(2H,s,H-4a). 13 C-NMR (100MHz, CD3OD)δ C:135.2(C-1′), 109.7(C-2′), 148.9(C-3′), 147.5(C-4′), 108.5(C-5′), 122.5(C-6′), 102.0 (3′-OCH2-4′), 175.8(C-2), 127.8(C-3), 164.7(C-4), 71.7(C-5), 47.1(C-3a), 57.7(C-4a).

[0086] Compound C2: Rostellulin A

[0087] Colorless feathery crystals (CHCl3), ESI-MS m / z: 495 [M+Na] + The molecular formula is C 25 H 28 O9. 1 H-NMR (400MHz, CDCl3)δ H :6.59(1H,s,H-2), 6.22(1H,s,H-5), 6.31(2H,s,H-2′,6′), 3.84(6H,s,3′,5′-OCH3), 5.48(1H,br s, OH-4′), 5.86 (1H, s, OCH2O), 5.85 (1H, s, OCH2O), 2.80 (2H, d, J = 6.4Hz, H-7), 3.78 (1H, d, J = 10.6H z, H-7′), 2.27 (1H, m, H-8), 1.97 (1H, m, H-8′), 4.19 (1H, dd, J=4.5, 11.2Hz, Ha-9), 4.03 (1H, m, Hb-9 ), 4.06 (1H, m, Ha-9′), 3.99 (1H, dd, J=3.6, 11.5Hz, Hb-9′), 2.07 (3H, s, H-11), 2.06 (3H, s, H-11′). 13 C-NMR (100MHz, CDCl3)δ C :132.4(C-1), 107.9(C-2), 146.0(C-3), 145.8(C-4), 109.3(C-5), 128.5(C- 6), 32.9(C-7), 35.4(C-8), 66.4(C-9), 133.5(C-1′), 105.8(C-2′, 6′), 147. 1(C-3′, 5′), 134.9(C-4′), 48.2(C-7′), 43.4(C-8′), 63.6(C-9′), 170.8 / 17 0.9 (C-10, 10′), 20.8 / 20.9 (C-11, 11′), 100.7 (OCH2O), 56.3 (3′, 5′-OCH3).

[0088] Compound C3: (+)-Pinoresinol

[0089] White powder, readily soluble in chloroform and acetone; turns deep red with concentrated sulfuric acid-vanillin; ESI-MS m / z: 357 [MH]. - The molecular formula is C 20 H 22 O6. 1 H-NMR (400MHz, Acetone-d6)δ H : 6.99 (2H, d, J = 1.7Hz, H-2, 2′), 6.80 (2H, d, J = 8.2Hz, H-5, 5′), 6.84 (2H, dd, J = 1.7, 8.2Hz, H-6, 6′), 4.67 (2H, d, J = 4.2Hz, H -7,7′), 4.20(2H,m,Ha-9,9′), 3.80(2H,m,Hb-9,9′), 3.08(2H,m,H-8,8′), 3.83(6H,s,3,3′-OCH3,7.56(2H,brs,OH-4,4′). 13 C-NMR (100MHz, Acetone-d6)δ C : 133.1 (C-1, 1′), 109.5 (C-2, 2′), 147.2 (C-3, 3′), 145.8 (C-4, 4′), 114.5 (C-5, 5′) , 118.6 (C-6, 6′), 85.6 (C-7, 7′), 54.2 (C-8, 8′), 71.1 (C-9, 9′), 55.2 (3, 3′-OCH3).

[0090] Compound C4: (-)-Syringaresinol

[0091] White powder, readily soluble in chloroform and acetone, positive for FeCl3 reaction, turns deep red with concentrated sulfuric acid-vanillin, ESI-MS m / z: 417 [MH] - The molecular formula is C 22 H 26 O8. 1 H-NMR (400MHz, DMSO-d6)δ H : 8.26 (2H, s, OH-4, 4′), 6.60 (4H, s, H-2, 2′, 6, 6′), 4.62 (2H, d, J = 4.2Hz, H-7, 7′), 4.17 (2H , m, Ha-9, 9′), 3.78 (2H, m, Hb-9, 9′), 3.06 (2H, m, H-8, 8′), 3.76 (12H, s, 3, 3′, 5, 5′-OCH3). 13C-NMR (100MHz, DMSO-d6)δ C : 131.4 (C-1, 1′), 103.6 (C-2, 2′, 6, 6′), 147.9 (C-3, 3′, 5, 5′), 134.8 (C-4, 4′), 85.3(C-7,7′), 53.6(C-8,8′), 71.1(C-9,9′), 56.3(3,3′,5,5′-OCH3).

[0092] Compound C5: (-)-Medioresinol

[0093] Colorless granular crystals (MeOH), readily soluble in acetone and methanol, positive for FeCl3, turns deep red with concentrated sulfuric acid-vanillin, ESI-MS m / z: 387 [MH] - The molecular formula is C 21 H 24 O7.

[0094] 1 H-NMR (400MHz, CD3OD)δ H : 6.94 (1H, d, J = 1.4Hz, H-2′), 6.76 (1H, d, J = 8.1Hz, H-5′), 6.80 (1H, dd, J = 1.4, 8.1Hz, H-6′), 6.64 (2H, s, H-2, 6), 4.70 (2H, d, J = 3 .9Hz, H-7, 7'), 4.23 (2H, m, Ha-9, 9'), 3.85 (2H, m, Hb-9, 9'), 3.13 (2H, m, H-8, 8'), 3.84 (3H, s, 3'-OCH3), 3.83 (6H, s, 3, 5-OCH3). 13 C-NMR (100MHz, CD3OD)δ C :133.1(C-1), 104.5(C-2,6), 149.3(C-3,5), 136.2(C-4), 133.8(C-1′), 110.9(C-2′), 149.2(C-3′),

[0095] 147.3(C-4′), 116.1(C-5′), 120.1(C-6′), 87.7(C-7), 55.6(C-8), 72.7(C-9 ), 87.5(C-7′), 55.3(C-8′), 72.6(C-9′), 55.5(3′-OCH3), 55.9(3,5-OCH3).

[0096] Compound C6: Epi-pinoresinol

[0097] White powder, readily soluble in acetone and methanol; turns deep red with concentrated sulfuric acid-vanillin; ESI-MS m / z: 357 [MH]. - The molecular formula is C 20 H 22 O6. 1 H-NMR (400MHz, CD3OD)δ H : 6.95 (2H, d, J = 8.7Hz, H-5, 5′), 6.75-6.8 (4H, m, H-2, 2′, 6, 6′), 4.84 (1H, d, J = 5.9Hz, H-7′), 4.40 (1H, d, J = 7.0Hz, H-7), 4.09 (1H, d, J = 9.3 Hz, Ha-9), 3.83 (1H, m, Hb-9), 3.77 (1H, m, Ha-9′), 3.26 (1H, m, Hb-9′), 3.37 (1H, m, H-8′), 2.92 (1H, m, H-8), 3.84 (3-OCH3), 3.85 (3′-OCH3). 13 C-NMR (150MHz, CD3OD)δ C : 133.9(C-1), 110.9(C-2), 149.1(C-3), 147.4(C-4), 116.1(C-5), 120.2(C-6), 131.4(C-1′), 110.6(C-2′), 148.9(C-3′), 146.7( C-4′), 116.0(C-5′), 119.4(C-6′), 89.4(C-7), 55.6(C-8), 72.0(C-9), 83.5(C-7′), 51.3(C-8′), 70.6(C-9′), 56.4(3′, 3-OCH3).

[0098] Example 3 Activity Test

[0099] 1. Experimental instruments and materials

[0100] Real-time quantitative PCR instrument, LightCycler 480II, Roche, Switzerland;

[0101] Cellmeter Auto 1000 cell counter, Nexcelom, USA;

[0102] Full-wavelength absorption microplate reader, CLARIOstarplus, BMG LABTECH, Germany;

[0103] Viral genome RNA extraction kit, DP315-R, Beijing Tiangen Biotech Co., Ltd.;

[0104] Bacterial total RNA extraction kit, DP430-H, Beijing Tiangen Biotech Co., Ltd.

[0105] HiScriptIII U+One Step qRT-PCR Probe Kit, Q225, Nanjing Novizan Biotechnology Co., Ltd.;

[0106] HiScript II One Step qRT-PCR SYBR Green Kit, Q221, Nanjing Novizan Biotechnology Co., Ltd.;

[0107] DMEM medium, C11995500BT, Gibco, USA;

[0108] Fetal bovine serum, 10099141C, Gibco, USA;

[0109] Penicillin-streptomycin solution (100×) 15140122, Gibco, USA;

[0110] Trypsin-EDTA 25200-056 Gibco, USA;

[0111] CCK-8 Reagent Kit E1008, Pulilai, China.

[0112] The Huh7 human liver cancer cells (from the China Center for Type Culture Collection, original laboratory records) and the SFTSV strain HBMC_human_2015 were donated by the Wuhan Institute of Virology, Chinese Academy of Sciences.

[0113] 2. Experimental Methods

[0114] 2.1 Cell Culture

[0115] (1) Cell resuscitation

[0116] Preheat the water bath to 37°C. Once the temperature reaches the specified level, remove the frozen cells from the liquid nitrogen tank. When thawing the cells, follow the principle of "slow freezing, rapid thawing." Wrap the cell cryopreservation tubes in PE gloves and quickly place them in the water bath, gently shaking to accelerate cell thawing. After thawing, transfer the cells to a 15mL centrifuge tube using a 1mL pipette. Add an appropriate amount of complete culture medium containing 10% FBS and 1% antibiotics, and mix thoroughly by pipetting. Centrifuge at 300×g for 5 minutes. After centrifugation, discard the cell supernatant, aspirate any remaining liquid from the tube opening, add an appropriate amount of complete culture medium containing 10% FBS and 1% antibiotics to resuspend the cell pellet, mix thoroughly by pipetting, and transfer to a T25 culture flask. Gently shake to ensure cell homogeneity and place in a 37°C CO2 incubator.

[0117] (2) Cell passage

[0118] Remove cells from the CO2 incubator and observe them under a microscope. When the cell confluence reaches 80%–90%, they can be passaged. For adherent cells, discard the culture medium in the flask with a pipette, add an appropriate amount of PBS, and wash twice. After washing, discard the PBS, add an appropriate amount of 0.25% trypsin, thoroughly wet the bottom of the flask with the trypsin, discard any residual trypsin with a pipette, and place the flask in a 37°C CO2 incubator for 2–3 minutes. Remove the flask and observe the cell digestion under a microscope. When the cells become rounded and the intercellular spaces increase, digestion is complete. Add an appropriate amount of DMEM complete medium containing 10% FBS and 1% antibiotics to stop digestion. Mix well by pipetting, then transfer an appropriate amount of cells to a new T25 culture flask, add complete medium containing 10% FBS and 1% antibiotics to a volume of about 5 mL, mix well by pipetting, and continue culturing in a 37°C CO2 incubator.

[0119] (3) Cell cryopreservation

[0120] Cells to be cryopreserved are removed from the CO2 incubator and observed under a microscope. When cell confluence reaches 80%–90%, cells can be cryopreserved. For adherent cells, discard the culture medium in the flask using a pipette, add an appropriate amount of PBS, wash twice, add an appropriate amount of 0.25% trypsin to thoroughly wet the bottom of the flask, discard any residual trypsin, and place in a 37°C CO2 incubator for 2–3 minutes. Observe the cell digestion under a microscope. When the cells become rounded and the intercellular spaces increase, digestion is complete. Add an appropriate amount of DMEM complete culture medium containing 10% FBS and 1% antibiotics to stop digestion. Mix well by pipetting and transfer to a 15mL centrifuge tube, centrifuge at 1000 rpm for 5 minutes. After centrifugation, discard the supernatant, aspirate the remaining liquid from the tube tip with a 1mL pipette tip, add an appropriate amount of PBS, mix well by pipetting, and centrifuge again at 300×g for 5 minutes. After centrifugation, discard the cell supernatant, aspirate any remaining liquid from the tube opening, add 1 mL of pre-prepared cryopreservation solution, mix well by pipetting, and transfer to cryopreservation tubes. Immediately place the cryopreservation tubes in a gradient cooling box and store them at -80°C. After 24 hours, transfer them to a liquid nitrogen tank, and label them (including cell name, cryopreservation date, passage number, and cryopreservation person), and record the information.

[0121] 2.2 Cell viability detection

[0122] The cytotoxicity of the test samples was detected using the CCK-8 assay. Huh7 cells in logarithmic growth phase were digested and then subjected to a 9 × 10⁻⁶ saturation index. 3Cells were seeded at a density of 100 μL per well in 96-well plates and incubated at 37°C, 5% CO2, and saturated humidity for 12–16 h. After cell attachment, the original culture medium was aspirated, and the cells were rinsed once with PBS buffer. Then, the test sample was diluted with DMEM (2% DMEM) containing 2% FBS and 1% penicillin-dextrose antibody. 100 μL of culture medium containing different concentrations of the compound was added to each well of the experimental group, setting up 8 concentration groups (final concentrations in wells: 20, 10, 5, 2.5, 1.25, 0.62, 0.31, 0.15 μM), with 6 replicates per concentration group. A blank control and a DMSO control group were also included. After 48 h of continuous culture under the above conditions, 10 μL of CCK-8 reagent was added to each well, and incubation was continued for 1–4 h under the same conditions. The absorbance (OD value) was measured at 450 nm using a microplate reader. The cell viability was calculated using the following formula:

[0123]

[0124] 2.3 Detection of viral load in cell culture supernatant and intracellular vRNA level

[0125] After digesting Huh7 cells in the logarithmic growth phase, they were subjected to 5 × 10⁻⁶... 4 Cells were seeded at a density of 10 cells / well in 48-well plates, with 3 replicates per group, and cultured overnight in an incubator at 37°C, 5% CO2, and saturated humidity. After cell attachment, the original culture medium was aspirated, and the cells were rinsed once with PBS buffer. SFTSV was then challenged at an MOI of 0.2 per well. The SFTSV strain was diluted with 2% DMEM containing the drug to form a composite virus solution. Two working concentrations were set for Acanthocephala extract and fractional extracts: 2.5 and 10 μg / mL. Two working concentrations were set for monomeric compounds: 2.5 and 10 μM. An infection group and a DMSO control group were also included. 250 μL of the composite virus solution was added to each well. Two hours after challenge, the composite virus solution was aspirated, and the cells were rinsed twice with PBS buffer. 250 μL of 2% DMEM was added to each well in the pure infection group, and 250 μL of 2% DMEM containing different drug concentrations was added to each well in the drug-treated groups. Morphological changes in Huh7 cells were recorded under a microscope at 24 and 48 hours post-infection. Cells were collected 48 hours after infection, and RNA was extracted.

[0126] The viral load and intracellular vRNA in the supernatant of infected Huh7 cells were quantitatively analyzed using qRT-PCR.

[0127] Sample collection: 48 h after infection, the supernatant was aliquoted into two portions. One portion (50 μL) was used for RNA extraction, and the other portion was frozen at -80 °C for later use. Cells were then rinsed with PBS buffer and 350 μL of lysis buffer was added to the wells to fully lyse the cells. The lysate was collected in 1.5 mL EP tubes and frozen at -80 °C.

[0128] RNA extraction from samples:

[0129] (1) Viral nucleic acid extraction: The collected 50 μL supernatant was used to extract viral RNA using the TIANamp Virus RNA Kit (Tiangen, catalog number DP315-R). The specific procedures are as follows:

[0130] ① Before use, bring the reagents and consumables that come with the kit to room temperature.

[0131] ② Reagent preparation: Add 310 μL of LNase-Free ddH2O to the tube containing 310 μg of Carrier RNA lyophilized powder. After complete dissolution, obtain a 1 μg / μL solution, and aliquot according to experimental requirements. Additionally, add 48 mL and 17 mL of anhydrous ethanol to the RW and GD solutions respectively, mix well, and label accordingly for later use.

[0132] ③ Prepare the Carrier RNA working solution according to the instructions. Add the Carrier RNA solution to the RL lysis buffer in a 100:1 volume ratio.

[0133] ④ In a biosafety cabinet, add 200 μL of carrier RNA working solution to 50 μL of virus solution, mix thoroughly, and incubate at room temperature for 10 min.

[0134] ⑤ Add 200 μL of anhydrous ethanol, vortex for 15 s, and centrifuge briefly. Collect the mixture onto the adsorption column, centrifuge at 8000 r / min for 1 min, and discard the waste liquid.

[0135] ⑥ Add 500 μL of GD solution, centrifuge at 8000 rpm for 1 min, and discard the waste liquid. Then add 500 μL of RW solution, centrifuge at 8000 rpm for 1 min, discard the waste liquid, and repeat twice.

[0136] ⑦ Replace with an empty sleeve, run the column at 12000r / min for 2 minutes to allow the adsorption column to dry completely, and discard the waste liquid.

[0137] ⑧ Transfer the adsorption column to a new RNase-free 1.5mL centrifuge tube, let it air dry at room temperature for about 3 minutes to allow the adsorption column to dry completely, add an appropriate amount of RNase-free ddH2O to elute, centrifuge at 8000r / min for 1 minute to obtain the RNA solution.

[0138] (2) Total RNA extraction from cells: Cellular nucleic acid was extracted using the RNAprep Pure Cell / Bacteria Kit (Tiangen, catalog number DP430-H). The specific procedures are as follows:

[0139] ① Before use, bring the reagents and consumables that come with the kit to room temperature.

[0140] ② Reagent preparation: Before operation, add β-mercaptoethanol to the RL lysis buffer to a final concentration of 1%, and prepare fresh each time. 70% anhydrous ethanol: Prepare using RNase-free water. Additionally, add 48 mL of anhydrous ethanol to the RW, mix well, and label it for later use.

[0141] ③ Add 350 μL of RL lysate with β-mercaptoethanol to the cell culture plate or cell pellet, mix well by pipetting, and then transfer to a CS filter column. Centrifuge at 12000 r / min for 2 min and collect the filtrate.

[0142] ④ Add 350 μL of 70% anhydrous ethanol to the filtrate and mix well. Transfer the liquid to a CR3 filter column, centrifuge at 12000 r / min for 1 min, and discard the waste liquid.

[0143] ⑤ Add 700 μL of RW1 to the filter column, centrifuge at 12000 r / min for 1 min, and discard the waste liquid.

[0144] ⑥ Add 500 μL of RW eluent to the filter column, centrifuge at 12000 rpm for 1 min, discard the waste liquid, and repeat twice. Replace with an empty sleeve, and run at 12000 rpm for 2 min to remove residual rinsing liquid from the adsorbent material.

[0145] ⑦ Transfer the adsorption column into a new RNase-Free ddH2O 1.5mL centrifuge tube, add an appropriate amount of RNase-Free water, let stand at room temperature for 2 min, centrifuge at 12000r / min for 2 min to obtain RNA solution.

[0146] 3. Experimental Results

[0147] 3.1 In vitro inhibition of SFTSV infection by Acanthus extract and its fractions

[0148] This study used Huh7 cells as a model and employed qRT-PCR to detect the RNA levels of SFTSV in cell culture supernatant and intracellular cells after SFTSV infection. The inhibitory effects of *Acanthopanax* extracts (60% ethanol extract Fr. 60% EtOH, ethyl acetate extract Fr. EtOAc, and n-butanol extract Fr. n-BuOH) on SFTSV infection were evaluated. The results showed that the viral genome copy number in the cell culture supernatant treated with Fr. 60% EtOH, Fr. EtOAc, and Fr. n-BuOH was significantly reduced (Table 1). Furthermore, at a concentration of 10 μg / mL, the SFTSV genome copy number in the cell culture supernatant of all three treatment groups was reduced by more than 10-fold (>1 log unit) compared to the untreated infection group (Control group), indicating that the three extracts effectively inhibited viral particle release. Furthermore, 48 hours after infection, the intracellular viral RNA (vRNA) level in the treated groups was significantly lower than that in the control group (Table 2). At a concentration of 10 μg / mL, the intracellular vRNA levels in all three sample treatment groups decreased by more than 95%, suggesting that the extract may exert potent anti-SFTSV activity by interfering with viral RNA replication. Among these, the ethanol extract showed significantly better results than the n-butanol extract in terms of intracellular vRNA levels.

[0149] Table 1. Viral genome copy number in each treatment group of the extract

[0150]

[0151] *** P<0.001

[0152] Table 2. Intracellular vRNA levels in each extract treatment group

[0153]

[0154] 3.2 The compound inhibits SFTSV infection in vitro.

[0155] This study used Huh7 cells as a model and employed qRT-PCR to detect the SFTSV RNA level in the cell culture supernatant after SFTSV infection, and to evaluate the inhibitory effect of lignan compounds (B1-B6, C1-C6) from *Acanthopanax* on SFTSV infection. The results showed that only B2, C2, and C5 significantly reduced the SFTSV viral genome copy number in the culture supernatant compared to the untreated control group (Table 3).

[0156] Table 3. Viral genome copy number in the compound treatment groups

[0157]

[0158]

[0159] * P<0.05, ** P<0.01, *** P<0.001.

[0160] Example 4: Cytotoxicity Experiment

[0161] The cytotoxicity of the aforementioned compounds that inhibit SFTSV on Huh7 cells was evaluated by microscopic morphological observation and the CCK-8 assay.

[0162] Microscopic morphological observation showed that cells treated with compound B2 at concentrations of 2.50 and 10.00 μM exhibited significant morphological changes, suggesting that the compound may have cytotoxic properties. Figure 1 ).

[0163] CCK-8 results showed that compound B2 exhibited strong cytotoxic activity at 10.00 μM.

[0164] (Table 4)

[0165] Table 4. Toxicity (survival rate) of compound-treated groups on Huh7 cells

[0166]

[0167] Example 5: Effect of Potentially Active Compounds on Intracellular vRNA Levels After SFTSV Infection

[0168] To further evaluate the inhibitory effects of compounds C2 and C5, which have no significant cytotoxicity, on SFTSV infection, Huh7 cells were used as a model, and the intracellular SFTSV vRNA level was detected by qRT-PCR. The results showed that compared with the untreated infection control group (Control group), compounds C2 and C5 at a concentration of 10 μM significantly reduced the intracellular vRNA level of SFTSV-infected cells (P<0.05) (Table 5), with intracellular vRNA levels decreasing by more than 80%.

[0169] Table 5. Intracellular vRNA levels in the compound-treated groups

[0170]

[0171] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A compound for fever with thrombocytopenia syndrome, or its pharmaceutically acceptable salt, solvate, tautomer, stereoisomer, prodrug molecule, or metabolite, wherein the compound is selected from:

2. The use of the compound as described in claim 1, or its pharmaceutically acceptable salts, solvates, tautomers, stereoisomers, prodrug molecules, or metabolites, characterized in that, Used to prepare a composition for fever with thrombocytopenia syndrome.

3. The use as described in claim 2, characterized in that, The treatment for fever with thrombocytopenia syndrome includes one or more of the following: (i) relief of high fever, thrombocytopenia, leukopenia and gastrointestinal symptoms; (ii) suppression of neurological symptoms, bleeding in multiple organ dysfunction and multiple organ injury; (iii) promotion of hematopoietic function and immune system reconstruction; (iv) anti-SFTSV infection.

4. The use as described in claim 2, characterized in that, The composition is a pharmaceutical composition.

5. The use as described in claim 2, characterized in that, The dosage form of the composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

6. The use as described in claim 5, characterized in that, The dosage form of the composition is tablets, capsules, soft capsules, gels, oral preparations, suspensions, granules, patches, ointments, pills, powders, injections, infusions, lyophilized injections, intravenous emulsions, liposome injections, suppositories, sustained-release preparations, or controlled-release preparations.

7. An active component for use in fever with thrombocytopenia syndrome, characterized in that, The active fraction is selected from ethanol extracts; wherein, the preparation method of the ethanol extract includes: Take the medicinal material of Acanthopanax and mix it with 60% ethanol aqueous solution. Reflux and extract at 90℃ for 2 hours. Repeat the extraction 3 times. Combine the three extracts and concentrate under reduced pressure until there is no alcohol taste.

8. The use of the active site as described in claim 7 in the preparation of a medicament for fever with thrombocytopenia syndrome.

9. A pharmaceutical composition comprising the active site as described in claim 7.

10. The pharmaceutical composition according to claim 9, characterized in that, The dosage form of the pharmaceutical composition is a solid dosage form, a semi-solid dosage form, or a liquid dosage form.

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