CN-121971467-A - Application of periplocin in preparation of anti-PRRSV (porcine reproductive and respiratory syndrome virus) drug

Abstract

The invention provides an application of periplocin in preparing a medicine for resisting PRRSV (porcine reproductive and respiratory syndrome virus), belonging to the technical field of antiviral medicines. The experimental result shows that the periplocin has extremely remarkable inhibiting and blocking effects on the-1-position ribosome frameshift (-1 Ribosomal Frameshifting) process of PRRSV virus, can effectively inhibit the replication of PRRSV virus and further inhibit the proliferation of PRRSV virus, has extremely remarkable inhibiting effects on the-1-position ribosome frameshift process of different strains of PRRSV virus, can effectively inhibit the replication and proliferation of PRRSV in vitro and in vivo, can be used for preparing products for inhibiting the proliferation of PRRSV, and can be used for preparing medicaments for treating and preventing diseases caused by PRRSV infection, and the medicaments are broad-spectrum anti-PRRSV medicaments and have wide application prospects.

Inventors

• BAI XIUFENG
• Zeng Nanfang
• Mou Dachao
• Dong Mengyi
• WU SHASHA
• TAN XIAO
• CHEN YANQIONG
• CHEN JING
• CHEN JIE

Assignees

• 巨星农牧有限公司

Dates

Publication Date

20260505

Application Date

20260310

Claims (10)

1. 1. The application of periplocin in preparing PRRSV virus resisting medicine is provided.
2. 2. Use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus for the prevention and/or treatment of porcine reproductive and respiratory syndrome caused by PRRSV virus infection.
3. 3. The use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus, wherein said medicament is a medicament for inhibiting replication and proliferation of PRRSV virus.
4. 4. Use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus comprising VR2332, JXA1, NADC30 and NADC34 strains.
5. 5. The use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus, wherein the medicament comprises periplocin and pharmaceutically acceptable excipients.
6. 6. Use of periplocin according to any one of claims 1 to 5 for the preparation of an anti-PRRSV virus drug, wherein said drug is an antiviral drug that inhibits the-1 ribosomal frameshift process of said PRRSV virus.
7. 7. The use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus, characterized in that the periplocin concentration in the medicament is 0.226-4.226 μm.
8. 8. Use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus, characterized in that the periplocin concentration in the medicament is 0.5 μm.
9. 9. The use of periplocin according to claim 1 for the preparation of a medicament against PRRSV virus, wherein said periplocin is used in an effective dose of 1mg/kg in a medicament against PRRSV virus in live pigs.
10. 10. The use of periplocin according to claim 1 for the preparation of anti PRRSV virus medicaments, wherein the medicaments are oral formulations, injections.

Description

Application of periplocin in preparation of anti-PRRSV (porcine reproductive and respiratory syndrome virus) drug Technical Field The invention belongs to the technical field of antiviral drugs, and particularly relates to application of periplocin in preparation of a PRRSV virus resistant drug. Background PRRSV is porcine reproductive and respiratory syndrome virus, an alias blue ear virus, belongs to arterivirus genus of arterividae, and is a single-strand positive strand RNA virus with envelope. The phenomenon of-1-position ribosome frameshift (-1 Ribosomal Frameshifting) during ribosome extension is common in RNA viruses, and has similar mechanisms not only in PRRSV but also in IBV (infectious bronchitis virus), HIV-1 (human immunodeficiency virus type 1), SARS virus (severe acute respiratory syndrome coronavirus) and other viruses. The process is specifically divided into three steps, firstly, the pseudo-junction structure in the mRNA forces the ribosome in the extension stage to stop, at this time the anticodon loops of the aminoacyl tRNA at the A site and the peptidyl tRNA at the P site just bind to the sliding sequence of the mRNA, secondly, the sliding sequence causes the tRNA to shift by-1 position, then the downstream mRNA pseudo-junction is opened, the ribosome continues to move forward, but the reading frame is changed. Studies have shown that the sliding sequence of PRRSV is "UUUAAAC", followed by a three-necked "pseudoknot" structural sequence that mediates ribosome withdrawal. When the ribosome moves to the sliding sequence, the tRNA is detached from the ribosome, which in a sliding manner reverses by one step, resulting in an open reading frame of "-1 Ribosomal Frameshifting", then the tRNA is repositioned, the peptide transfer center is unaffected, the nascent peptide chain does not detach, and the ribosome continues into the translation process of ORF1 b. The mechanism has the advantages of simple genome, high replication speed and high utilization rate of genetic materials, thereby promoting the rapid propagation of the virus in host cells. If the-1 Ribosomal Frameshifting process of PRRSV can be inhibited, the replication of PRRSV can be blocked, so as to attain the goal of inhibiting virus proliferation. Therefore, research on drugs capable of effectively inhibiting the-1 Ribosomal Frameshifting process of PRRSV is of great importance in developing drugs against PRRSV or for treating blue-pig ear disease caused by PRRSV. Disclosure of Invention In view of the above, the invention aims to provide an application of periplocin in preparing a PRRSV virus resistant drug. The technical scheme provided by the invention is as follows: The application of periplocin in preparing PRRSV virus resisting medicine is provided. Periplocin (Periplocoside) is a cardiac glycoside compound, and has the effects of tonifying heart and promoting urination, and can be used for enhancing heart contractility by inhibiting myocardial cell membrane Na +,K+ -ATPase and improving left ventricular function. The molecular formula of periplocin is C 36H56O13; the structural formula of periplocin is: 。 Further, the medicament is used for preventing and/or treating porcine reproductive and respiratory syndrome caused by PRRSV virus infection. Further, the drug is a drug for inhibiting replication and proliferation of PRRSV virus. Further, the PRRSV virus includes VR2332, JXA1, NADC30 and NADC34 strains. Further, the medicine comprises periplocin and pharmaceutically acceptable auxiliary materials. Further, the drug is an antiviral drug that inhibits the-1 ribosomal frameshift process of the PRRSV virus. Further, the concentration of the periplocin in the medicine is 0.226-4.226 mu M. Further, the concentration of periplocin in the drug is 0.5 μm. Further, the effective dose of periplocin in the application of the anti-PRRSV virus medicament in the living pigs is 1mg/kg. Further, the medicine is an oral preparation or an injection. Compared with the prior art, the invention has the beneficial effects that: The application discovers a new application of periplocin in inhibiting PRRSV virus. Experiments prove that the periplocin has extremely high remarkable inhibiting effect on the-1-position ribosome frameshift (-1 Ribosomal Frameshifting) process of PRRSV virus, can effectively inhibit the replication of PRRSV virus and further inhibit the proliferation of PRRSV virus, has the CC50 of 4.226 mu M on MARC-145 cells, has the half concentration of 0.226 mu M on the-1-position ribosome frameshift process of PRRSV virus, has no toxicity on wild type MARC-145 cells, has extremely high remarkable inhibiting effect on the-1-position ribosome frameshift process of PRRSV virus due to the minimum effective concentration of 0.5 mu M, has extremely high remarkable inhibiting effect on the proliferation of PRRSV virus due to the 1mg/kg dose of periplocin, has extremely high remarkable inhibiting effect on the-1-position ribosome frame