阅读说明：本技术 一种小分子化合物ml-sa1的应用 (Application of small molecular compound M L-SA 1 ) 是由 徐国东 刘愈杰 曹志贱 郑从义 于 2019-12-24 设计创作，主要内容包括：本发明提供了一种小分子化合物ML-SA1在制备抗病毒药物中的应用。该发明通过在A549细胞和huh7细胞两种细胞系内,小分子化合物ML-SA1均以浓度依赖的方式抑制细胞内病毒RNA转录水平和E蛋白的表达水平,表明小分子ML-SA1在一定浓度梯度范围内对ZIKV和DENV-2的抑制效应不具有细胞特异性,而且小分子ML-SA1通过作用早期进入阶段发挥抗病毒效应,其抗ZIKV效应不依赖于病毒的滴度且不影响TRPML2蛋白的转录水平；另外,通过CCK-8法检测表明小分子化合物ML-SA1在抗病毒活性浓度梯度内无细胞毒性。(The invention provides an application of a small molecule compound M L-SA 1 in preparation of antiviral drugs, wherein in two cell lines of A549 cells and huh7 cells, the small molecule compound M L-SA 1 inhibits the transcription level of virus RNA and the expression level of E protein in cells in a concentration-dependent manner, so that the inhibition effect of the small molecule M L-SA 1 on ZIKV and DENV-2 in a certain concentration gradient range does not have cell specificity, the small molecule M L-SA 1 plays an antiviral effect in an early entry stage through action, the ZIKV resistant effect does not depend on the titer of viruses and does not influence the transcription level of TRPM L2 protein, and in addition, the detection of a CCK-8 method shows that the small molecule compound M L-SA 1 has no cytotoxicity in an antiviral activity concentration gradient.)

1. An application of a small molecular compound M L-SA 1 in preparing antiviral drugs.

2. The use of claim 1, wherein: the virus is Zika virus and dengue virus.

3. The use according to claim 2, wherein the concentration of the small molecule compound M L-SA 1 having the anti-Zika virus activity is 50-400. mu.M.

4. The use according to claim 2, wherein the concentration of the small molecule compound M L-SA 1 having anti-dengue virus activity is 10-400. mu.M.

5. The use of claim 1, wherein the antiviral drug comprises an active ingredient and a pharmaceutically acceptable excipient, wherein the active ingredient comprises the small molecule compound M L-SA 1.

Technical Field

The invention belongs to the technical field of biology, and particularly relates to application of a small molecular compound M L-SA 1.

Background

Zika virus (ZIKV) belongs to the flaviviridae family of flaviviridae and is transmitted mainly by arboviruses, but also from person to person by intercourse and placenta. Since 2007, Zika epidemic has developed in great continents and rapidly spread to 66 countries and regions, and more studies have shown that Zika virus infection is closely related to neonatal microcephaly and adult Guillain-Barre syndrome, in addition to typical symptoms caused by flaviviruses such as fever, rash, joint pain, and muscle weakness. However, no effective vaccine or clinical drug is currently available for the treatment of Zika virus.

With the progress of research, more and more specific target small molecule inhibitors are gradually discovered, such as E protein inhibitors against the virus's own proteins, RNA polymerase inhibitors and methyltransferase inhibitors acting on NS5, protease inhibitors acting on NS2B-NS3 complex, etc. (trexiangling et al, 2018), wherein NS5 RdRp, the key enzyme for replication, is the most promising target for studying viral inhibitors, such as Zmurko J, infecting AG129 mice with ZIKV, 7-deaza-2 ' -C-methyladenosine (7DMA) was found to be effective in inhibiting replication of zika (Zmurko J et al, 2016), L u G et al found that 2 ' -C-methyl and 2 ' -C-ethynyl substituted 5 ' -triphosphates could be effective in inhibiting RNA polymerase activity (L u G et al, 2017), such as nucleotide analog nittd008, although RNA can be used as a small molecule inhibitor polymerase target, new antiviral small molecule inhibitors are still being developed because of drug resistance and cytotoxicity.

Disclosure of Invention

The invention aims to solve the problems that the existing antiviral micromolecules have drug resistance and cytotoxicity and are not beneficial to the research of antiviral drugs.

Therefore, the invention provides application of a small molecular compound M L-SA 1 in preparation of an antiviral drug.

Further, the virus is Zika virus and dengue virus.

Furthermore, the concentration of the anti-Zika virus activity of the small molecule compound M L-SA 1 is 50-400 mu M.

Furthermore, the concentration of the anti-dengue virus activity of the small molecule compound M L-SA 1 is 10-400 mu M.

The antiviral drug comprises an active ingredient and pharmaceutically acceptable auxiliary materials, wherein the active ingredient comprises a small molecule compound M L-SA 1.

The small molecular compound M L-SA 1(CAS:332382-54-4) is a TRPM L channel specific activator, and the chemical structural formula is as follows:

the invention has the beneficial effects that:

the small molecule compound M L-SA 1 is used as a host cell TRPM L channel specific activator, the target of action is not virus, so the virus can not generate drug resistance to the small molecule drug theoretically, in two cell lines of A549 cells and huh7 cells, the small molecule compound M L-SA 1 can inhibit the RNA transcription level and the expression level of E protein of intracellular viruses (Zika virus ZIKV and dengue virus DENV-2) in a concentration-dependent mode, the small molecule M L-SA 1 has no cell specificity to the inhibition effect of the ZIKV and the DENV-2 in a certain concentration gradient range, the small molecule M L-SA 1 plays an antiviral effect in an early entry stage through action, the anti-ZIKV effect does not depend on the titer of the viruses and does not influence the transcription level of the TRPM L2 protein, and the CCK-8 method detection shows that the small molecule compound M L-SA 1 has no cytotoxicity in an antiviral active concentration gradient.

The present invention will be described in further detail below with reference to the accompanying drawings.

Drawings

FIG. 1 is a graph showing the effect of small molecule M L-SA 1 on viral infection in A549 cells in the present invention;

FIG. 2 is a graph showing the effect of small molecule M L-SA 1 in huh7 cells on viral infection in the present invention;

FIG. 3 is a graph showing the effect of small molecule M L-SA 1 on cytotoxicity in the present invention;

FIG. 4 is a graph of the antiviral effect of small molecule M L-SA 1 on multiplicity of infection by different Zika viruses of the present invention;

FIG. 5 is a graph of the antiviral effect of small molecule M L-SA 1 at various stages in the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.