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巴西詹代拉蜜蜂蜂胶中黄酮类化合物对寨卡病毒和登革热病毒的抗病毒活性

Antiviral Activity of Flavonoids from Geopropolis of the Brazilian Jandaira Bee against Zika and Dengue Viruses.

作者信息

Silva Poliana Gomes da, Chaves Elton José Ferreira, Silva Tania Maria Sarmento, Rocha Gerd Bruno, Dantas Willyenne Marília, Oliveira Ronaldo Nascimento de, Pena Lindomar José

机构信息

Laboratory of Virology and Experimental Therapy (Lavite), Department of Virology, Aggeu Magalhães Institute (IAM), Oswaldo Cruz Foundation (Fiocruz), Recife 50670-420, Pernambuco, Brazil.

Phytochemical Bioprospecting Laboratory, Department of Chemistry, Federal Rural University of Pernambuco, Recife 52171-900, Pernambuco, Brazil.

出版信息

Pharmaceutics. 2023 Oct 19;15(10):2494. doi: 10.3390/pharmaceutics15102494.

Abstract

Arthropod-borne viruses within the family such as Zika (ZIKV) and dengue (DENV) are responsible for major outbreaks in tropical countries, and there are no specific treatments against them. Naringenin and 7--methyl naringenin are flavonoids that can be extracted from geopropolis, a natural material that the Brazilian Jandaira stingless bee (Melipona subnitida Ducke) produces to protect its nest. Here, these flavonoids were tested against ZIKV and DENV using Vero cells as a cellular model to perform a cytotoxicity assay and to define the effective concentrations of TCID as the readout method. The results demonstrated the antiviral activity of the compounds against both viruses upon the treatment of infected cells. The tested flavonoids had antiviral activity comparable with 6-methylmercaptopurine riboside (6-MMPr), used here as a positive control. In addition, to identify the possible action mechanism of the antiviral candidates, we carried out a docking analysis followed by a molecular dynamics simulation to elucidate naringenin and 7--methyl naringenin binding sites to each virus. Altogether, these results demonstrate that both flavonoids have potent antiviral effects against both viruses and warrant further trials.

摘要

该病毒科中的节肢动物传播病毒,如寨卡病毒(ZIKV)和登革热病毒(DENV),是热带国家重大疫情的罪魁祸首,且尚无针对它们的特效治疗方法。柚皮素和7 - 甲基柚皮素是黄酮类化合物,可从巴西詹代拉无刺蜂(Melipona subnitida Ducke)为保护蜂巢而产出的天然物质地蜂胶中提取。在此,以Vero细胞作为细胞模型,使用这些黄酮类化合物针对寨卡病毒和登革热病毒进行测试,以进行细胞毒性测定,并将半数组织培养感染剂量(TCID)的有效浓度作为读数方法进行确定。结果表明,在处理受感染细胞后,这些化合物对两种病毒均具有抗病毒活性。所测试的黄酮类化合物具有与6 - 甲基巯基嘌呤核苷(6 - MMPr)相当的抗病毒活性,此处6 - MMPr用作阳性对照。此外,为确定抗病毒候选物可能的作用机制,我们进行了对接分析,随后进行分子动力学模拟,以阐明柚皮素和7 - 甲基柚皮素与每种病毒的结合位点。总之,这些结果表明,这两种黄酮类化合物对两种病毒均具有强大的抗病毒作用,值得进一步试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b52a/10609720/99e40a8be2e2/pharmaceutics-15-02494-g001.jpg

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