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盐酸美金刚:一种可能对抗基孔肯雅病毒的药物?

Memantine hydrochloride: a drug to be repurposed against Chikungunya virus?

机构信息

Institute of Chemistry, University of Campinas-UNICAMP, Campinas, SP, 13083-871, Brazil.

Laboratory of Virology, Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, MG, 38405-302, Brazil.

出版信息

Pharmacol Rep. 2021 Jun;73(3):954-961. doi: 10.1007/s43440-021-00216-4. Epub 2021 Feb 1.

Abstract

BACKGROUND

Chikungunya fever is an endemic disease caused by the Chikungunya virus (CHIKV) to which there is no vaccine or effective antiviral drug treatment so far. Our study aimed to evaluate the potential anti-CHIKV activity of memantine hydrochloride (mtnH), a drug from the class of the aminoadamantanes approved for the treatment of Alzheimer´s disease, as a possible drug to be repurposed to the treatment of Chikungunya fever.

METHODS

MtnH antiviral activity against CHIKV was determined by infecting BHK-21 cells with CHIKV-nanoluc, a virus carrying the marker nanoluciferase reporter, in the presence or absence of mtnH at concentrations ranging from 500 to 1.45 µM. The effective concentration of 50% inhibition (EC) was calculated. Cell viability assay (determination of CC) was also performed employing BHK-21 cells. Mutagenic assays were performed by the Salmonella Typhimurium/microsome assay (Ames test).

RESULTS

MtnH presented a CC of 248.4 ± 31.9 µM and an EC of 32.4 ± 4 µM against CHIKV in vitro. The calculated selectivity index (SI) was 7.67. MtnH did not induce genetic mutation in Salmonella strains with or without an external metabolizing system.

CONCLUSION

With the data herein presented, it is possible to hypothesize mtnH as a viable candidate to be repurposed as an anti-CHIKV drug. Clinical assays are, therefore, encouraged due to the promising in vitro results. The drug memantine hydrochloride is herein personified with a doubt: as a prior regulated drug against Alzheimer, could it follow the path against Chikungunya virus too?

摘要

背景

基孔肯雅热是一种由基孔肯雅病毒(CHIKV)引起的地方病,目前尚无疫苗或有效的抗病毒药物治疗方法。我们的研究旨在评估盐酸美金刚(mtnH)作为一种可能的抗 CHIKV 药物的潜在活性,盐酸美金刚是一种批准用于治疗阿尔茨海默病的金刚烷胺类药物,可作为治疗基孔肯雅热的药物重新利用。

方法

在存在或不存在浓度范围为 500 至 1.45 µM 的 mtnH 的情况下,用携带纳米荧光素酶报告基因的 CHIKV-nanoluc 感染 BHK-21 细胞,测定 mtnH 对 CHIKV 的抗病毒活性。计算 50%有效浓度(EC)。还使用 BHK-21 细胞进行细胞活力测定(确定 CC)。通过沙门氏菌 Typhimurium/微粒体测定(Ames 试验)进行诱变试验。

结果

mtnH 对 CHIKV 的 CC 为 248.4 ± 31.9 µM,EC 为 32.4 ± 4 µM。计算的选择性指数(SI)为 7.67。mtnH 未在有或没有外部代谢系统的沙门氏菌菌株中诱导遗传突变。

结论

根据本文提供的数据,可以假设 mtnH 是一种可行的抗 CHIKV 药物重新利用的候选药物。因此,由于体外结果有希望,鼓励进行临床检测。盐酸美金刚药物在这里被拟人化了:作为一种先前针对阿尔茨海默病的管制药物,它是否也能对抗基孔肯雅病毒?

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d96/7848042/3becfcb7a6a7/43440_2021_216_Fig1_HTML.jpg

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