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Anti-RNA (Ribonucleic Acid) virus medicine and application thereof

A RNA virus and drug technology, applied in the field of treatment of viral infections, can solve the problems of long time, high research and development costs, lack of predictability, etc.

Pending Publication Date: 2021-10-01
EAST CHINA UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this antiviral drug can achieve high specificity and selectivity, long-term and large-scale use often leads to drug resistance, and the cost of research and development is high and time-consuming, and lacks predictability

Method used

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  • Anti-RNA (Ribonucleic Acid) virus medicine and application thereof
  • Anti-RNA (Ribonucleic Acid) virus medicine and application thereof
  • Anti-RNA (Ribonucleic Acid) virus medicine and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0112] Embodiment 1. The inhibitory activity and cytotoxicity evaluation of the compound of the present invention to 2019 new coronavirus (2019-nCoV), Ebola virus, avian influenza virus A / GuangZhou / 99 (H9N2)

[0113] Materials and Methods:

[0114] Both leflunomide and teriflunomide are commercially available with a purity of over 98%.

[0115] Detection methods and results:

[0116] 1. Fluorescent quantitative PCR method to detect the efficacy experiment of anti-2019 novel coronavirus:

[0117] On Vero E6 cells (ATCC-1586) with 2019BetaCoV / Wuhan / WIV04 / 2019 strain (isolated by Wuhan Institute of Virology, Chinese Academy of Sciences, Zhou, P., et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020) infected with an infection amount of MOI=0.03 or MOI=0.05, at the same time adding different dilutions of the drug for co-culture, the drug was diluted with DMSO, and the DMSO dilution was used as a control. The infection solution was DMEM...

Embodiment 2

[0136] Embodiment 2. The antiviral activity evaluation of the combination of the compound of the present invention and other antiviral drugs

[0137] The inventors further tested leflunomide, teriflunomide and other antiviral drugs of the prior art, including lopinavir, ritonavir, ribavirin, remdesivir, oseltamivir , Tamiflu, laninamivir, peramivir and chloroquine (chloroquine phosphate) in one or more combinations.

[0138] It was found that the combination of leflunomide and teriflunomide with these antiviral drugs can produce better therapeutic effect; (Chloroquine phosphate) combined treatment effect is relatively better.

Embodiment 3

[0139] Example 3. Drug efficacy evaluation of leflunomide against influenza virus in mouse infection model

[0140] Experimental Materials:

[0141] Leflunomide is commercially available with a purity of over 98%.

[0142] Detection method:

[0143] In this experiment, the anti-influenza efficacy of the drug was evaluated based on the mouse influenza A / WSN / 33 (H1N1) infection model. The mice used were BALB / c female mice, 6-8 weeks old, weighing 18-22g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., and all animal experiments were performed in the ABSL-2 laboratory. After the mice adapted to the ABSL-2 environment for 2-3 days, the experiment was carried out, and the mice were divided into the following 4 groups: model group: Non-treatment; positive control group: Osel (oseltamivir) 20mg / kg; experimental group: Lef ( Leflunomide) 20mg / kg and 10mg / kg; 3 to 6 rats in each group. With A / WSN / 33(H1N1)2LD 50 =2000pfu / toxic dose carried out nasal d...

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Abstract

The invention discloses application of a compound shown in a formula I or pharmaceutically acceptable salt thereof in a medicine for treating RNA virus infection. The medicine / broad-spectrum and excellent anti-RNA virus activity, and have low toxicity to normal cells.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry; Specifically, the present invention leflunomide, teriflunomide etc. are used in the preparation of the medicine for treating RNA virus infection and in the treatment of virus infection. Background technique [0002] Diseases caused by virus infection are an important threat to public health security. These viruses include not only the well-known influenza virus, Ebola virus, bunya virus, avian influenza virus H9N2, H1N1, H7N9, arenavirus, rabies virus, HCV, HBV, HIV-1, HSV-1, HSV-2, etc., also include coronaviruses such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and 2019 novel coronavirus ( 2019-nCoV). [0003] Coronaviruses (Coronaviruses) are a large family that exists widely in nature. Humans and various animals are susceptible to them. Coronaviruses belong to the Coronaviridae family. Based on the systemati...

Claims

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Application Information

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IPC IPC(8): A61K31/42A61K31/277A61P31/14
CPCA61K31/42A61K31/277A61P31/14A61P31/18A61P31/16Y02A50/30
Inventor 李洪林徐可赵振江
Owner EAST CHINA UNIV OF SCI & TECH
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