Application of icariin I in the preparation of antiviral drugs

Abstract

The present invention discloses an application of icariin I or a pharmaceutical salt thereof in the preparation of an antiviral drug. The virus refers to Kaposi's sarcoma-associated herpes virus. The drug small molecule icariin I screened from a natural product library can significantly inhibit the lytic replication of KSHV, and the present invention provides a new solution for the treatment of KSHV.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to an application of icariin I in the preparation of antiviral drugs. Background Art

[0002] Herpes virus is a type of virus with an envelope and a double-stranded DNA genome. Currently, there are 8 types of herpes virus that can infect humans, of which KSHV and EBV belong to γ-herpes virus. After the initial infection, the herpes virus enters a latent infection period and is a lifelong carrier. Under certain conditions, the virus is activated and enters a lytic replication period, which can cause tumors and other diseases.

[0003] Kaposi's sarcoma-associated herpesvirus (KSHV) is an important human tumor virus, which is closely related to the occurrence of malignant diseases such as Kaposi's sarcoma (KS), primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). Among them, Kaposi's sarcoma is a common tumor and cause of death in AIDS patients. At present, there is a lack of highly effective antiviral drugs. Summary of the invention

[0004] The purpose of the present invention is to provide an application of icariin I in the preparation of antiviral drugs.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0006] The first aspect of the present invention provides a use of icariin I or a pharmaceutically acceptable salt thereof in the preparation of an antiviral drug.

[0007] The virus is Kaposi's sarcoma-associated herpesvirus (KSHV).

[0008] The pharmaceutically acceptable salt is an acid addition salt formed by icariin I and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid, succinic acid, fumaric acid, salicylic acid, phenylacetic acid or mandelic acid.

[0009] The present invention also provides a pharmaceutical preparation prepared from icariin I or its pharmaceutical salt and medically acceptable adjuvants or other pharmaceutically acceptable ingredients.

[0010] The dosage form of the pharmaceutical preparation is selected from powders, tablets, granules, capsules, solutions, emulsions, and suspensions.

[0011] The CAS number of the icariin I is 56725-99-6, and the structure is shown below (Pan C, Fujiwara Y, Horlad H, Shiraishi D, Iriki T, Tsuboki J, Ikeda T, Komohara Y. Flavonoid Compounds Contained in Epimedii Herba Inhibit Tumor Progression by Suppressing STAT3 Activation in the Tumor Microenvironment. Front Pharmacol. 2020 Mar 18; 11: 262. doi: 10.3389 / fphar.2020.00262. PMID: 32256354; PMCID: PMC7093601.):

[0012]

[0013] The present invention provides an application of icariin I or a pharmaceutically acceptable salt thereof in the preparation of an antiviral drug, wherein the icariin I is used as a single active ingredient.

[0014] Due to the adoption of the above technical solution, the present invention has the following advantages and beneficial effects:

[0015] The small molecule drug icariin I screened from a natural product library in the present invention can significantly inhibit the lysis and replication of KSHV. The present invention provides a new solution for the treatment of KSHV. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 This is a schematic diagram of the growth curve results of KSHV in the lytic replication phase in Example 1.

[0017] Figure 2 This is a schematic diagram of the fitting curve results of the small molecule ICSI inhibiting viral replication in Example 1. DETAILED DESCRIPTION

[0018] In order to explain the present invention more clearly, the present invention is further described below in conjunction with preferred embodiments. It should be understood by those skilled in the art that the following specific description is illustrative rather than restrictive, and should not be used to limit the scope of protection of the present invention.

[0019] Example 1

[0020] iSLK.219 cells constructed by Dr. Don Ganem's Lab were used as a cell model for screening KSHV antiviral drugs. iSLK.219 cells carry recombinant KSHV.219 virus. The viral genome contains a constitutive GFP reporter gene and an RFP reporter gene expressed by DOX-induced RTA, which helps to detect the latent infection and lytic replication activities of the virus. DOX and NaB were added to induce iSLK.219 cells to enter the lytic replication state, and the supernatant was collected to detect the number of viral particle copies to detect the replication of the virus. The results are shown in Figure 1 As shown, Figure 1 This is a schematic diagram of the growth curve results of KSHV in the lytic replication phase in Example 1. Figure 1 It was shown that iSLK.219 cells entered the KSHV virus lytic replication state after induction with DOX and NaB. The supernatant virus particles were collected and viral DNA was extracted. It was found that the replication of KSHV showed an upward trend with the extension of induction time.

[0021] DMSO was used to dilute icariin I (abbreviated as ICSI) to prepare a 1000× stock solution. The working concentrations of ICSI were 60 μM, 40 μM, 10 μM, 1 μM, 0.1 μM, 0.05 μM, 0.01 μM, 0.001 μM, and 0 μM (as a control).

[0022] iSLK.219 cells were seeded in a 96-well cell plate, with approximately 4 × 10 cells per well. 4 Cells were cultured for 24 hours until the cell density reached 90%, and then replaced with a cell culture medium containing 1 μg / μL DOX and 1 mM NaB. At the same time, the prepared 1000× stock solution was added to the culture medium in proportion to the set drug working concentration. The culture was continued in a cell culture incubator for 48-72 hours. The 96-well cell culture plate was removed, the cell supernatant was collected, and viral DNA was extracted. The ICSI inhibition ratio of viral replication was calculated and a curve was drawn to calculate the drug IC 50 The result is 2.402μM. Figure 2 As shown, Figure 2 This is a schematic diagram of the fitting curve results of the small molecule ICSI inhibiting viral replication in Example 1. Figure 2 The results showed that as the ICSI drug concentration increased, the inhibitory effect on KSHV virus replication was greater, and the drug concentration required to inhibit the virus by 50% was 2.402 μM.

[0023] The above is only a preferred embodiment of the present invention, and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment, it is not used to limit the present invention. Any technician familiar with this patent can make some changes or modify the technical contents suggested above into equivalent embodiments without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the solution of the present invention.

Claims

1. A use of icariin I or a pharmaceutically acceptable salt thereof as the sole active ingredient in the preparation of an antiviral drug, characterized in that: The virus is Kaposi's sarcoma-associated herpes virus.

2. The use of icariin I or a pharmaceutically acceptable salt thereof in the preparation of antiviral drugs according to claim 1, characterized in that: The pharmaceutically acceptable salt is an acid addition salt formed by icariin I and the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, lactic acid, citric acid, phosphoric acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenesulfonic acid, tartaric acid, pyruvic acid, acetic acid, maleic acid, succinic acid, fumaric acid, salicylic acid, phenylacetic acid or mandelic acid.

3. The use of icariin I or a pharmaceutically acceptable salt thereof in the preparation of antiviral drugs according to claim 1, characterized in that: The pharmaceutical preparation is prepared from the icariin I or its pharmaceutical salt and medically acceptable adjuvants or other pharmaceutically acceptable ingredients.

4. The use of icariin I or a pharmaceutically acceptable salt thereof in the preparation of an antiviral drug according to claim 3, characterized in that: The dosage form of the pharmaceutical preparation is selected from powders, tablets, granules, capsules, solutions, emulsions, and suspensions.

5. The use of icariin I or a pharmaceutically acceptable salt thereof in the preparation of antiviral drugs according to claim 1, characterized in that: The CAS number of the icariin I is 56725-99-6, and the structure is shown below:

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