β-烯酰胺酯衍生物在体外和硅学中对马雅洛病毒表现出良好的抗病毒潜力

IF 2.3 3区 生物学 Q3 MICROBIOLOGY
Natasha Cristina da Rocha, Leonardo dos Santos Corrêa Amorim, Vitor Won-Held Rabelo, Carolina Oliveira da Silva, Luciene Soares Silva, Geicy Kelly Pires Barboza, Mariana Falcão Lopes Princisval Carlos, Aurea Echevarria Aznar Neves Lima, Izabel Christina Nunes de Palmer Paixão
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引用次数: 0

摘要

玛雅罗病毒(MAYV)是玛雅罗热的病原体,其主要特征是急性发热和长期严重关节痛,这是其他虫媒病毒感染的常见表现,因此正确诊断是一项挑战。此外,在南美洲,尤其是巴西,也有马雅洛热病毒感染的报道。然而,由于缺乏疫苗或特异性抗病毒药物来控制这些感染,因此迫切需要寻找新的抗病毒药物。在此,我们采用体外和硅学策略评估了合成β-烯酰胺酯衍生物对 MAYV 复制的抗病毒潜力及其药代动力学和毒理学(ADMET)特性。为此,用 MOI 为 0.1 的 MAYV 感染 Vero 细胞,用化合物(50 µM)处理 24 小时,并通过斑块还原测定法量化病毒滴度。化合物 2b (83.33%) 和 2d (77.53%) 的活性最高,抑制率分别为 83.33% 和 77.53%。活性最高的化合物 2b(EC50 = 18.92 µM;SI >;52.85)和 2d(EC50 = 14.52 µM;SI >;68.87)比对照药物舒拉明(EC50 = 38.97 µM;SI >;25.66)表现出更高的效力和选择性。然后,我们研究了最活跃化合物的作用机制。所有化合物都没有杀病毒活性,也没有抑制病毒的吸附,但化合物 2b 抑制了病毒的进入(62.64%)。此外,化合物 2b 和 2d 还抑制了与新病毒颗粒释放有关的一些过程。最后,硅学研究结果表明,最有活性的化合物具有良好的 ADMET 参数,这增强了它们作为抗 MAYV 候选药物的前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

β-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus

β-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus

β-enaminoester derivatives exhibit promising in vitro and in silico antiviral potential against Mayaro virus

Mayaro virus (MAYV) is the causative agent of Mayaro fever, which is characterized mainly by acute fever and long-term severe arthralgia, common manifestations of other arbovirus infections, making the correct diagnosis a challenge. Besides, MAYV infections have been reported in South America, especially in Brazil. However, the lack of vaccines or specific antiviral drugs to control these infections makes the search for new antivirals an urgent need. Herein, we evaluated the antiviral potential of synthetic β-enaminoesters derivatives against MAYV replication and their pharmacokinetic and toxicological (ADMET) properties using in vitro and in silico strategies. For this purpose, Vero cells were infected with MAYV at an MOI of 0.1, treated with compounds (50 µM) for 24 h, and virus titers were quantified by plaque reduction assays. Compounds 2b (83.33%) and 2d (77.53%) exhibited the highest activity with inhibition rates of 83.33% and 77.53%, respectively. The most active compounds 2b (EC50 = 18.92 µM; SI > 52.85), and 2d (EC50 = 14.52 µM; SI > 68.87) exhibited higher potency and selectivity than the control drug suramin (EC50 = 38.97 µM; SI > 25.66). Then, we investigated the mechanism of action of the most active compounds. None of the compounds showed virucidal activity, neither inhibited virus adsorption, but compound 2b inhibited virus entry (62.64%). Also, compounds 2b and 2d inhibited some processes involved with the release of new virus particles. Finally, in silico results indicated good ADMET parameters of the most active compounds and reinforced their promising profile as drug candidates against MAYV.

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来源期刊
Archives of Microbiology
Archives of Microbiology 生物-微生物学
CiteScore
4.90
自引率
3.60%
发文量
601
审稿时长
3 months
期刊介绍: Research papers must make a significant and original contribution to microbiology and be of interest to a broad readership. The results of any experimental approach that meets these objectives are welcome, particularly biochemical, molecular genetic, physiological, and/or physical investigations into microbial cells and their interactions with their environments, including their eukaryotic hosts. Mini-reviews in areas of special topical interest and papers on medical microbiology, ecology and systematics, including description of novel taxa, are also published. Theoretical papers and those that report on the analysis or ''mining'' of data are acceptable in principle if new information, interpretations, or hypotheses emerge.
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